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1.
Neurosci Lett ; 704: 57-61, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-30951799

RESUMO

Although olfactory dysfunction is an early warning sign of Alzheimer's and Parkinson's diseases, and is commonly present in a range of other neurodegenerative disorders, the mechanisms for its pathogenesis are not yet clear. Since fMRI allows the mapping of spatial and temporal patterns of activity in multiple brain regions simultaneously, it serves as a powerful tool to study olfactory dysfunction in animal models of neurodegenerative diseases. Nonetheless, there have been no reports to date of mapping odor-induced activation patterns beyond the olfactory bulb to the extended networks of olfactory and limbic archicortex, likely due to the small size of the mouse brain. Therefore, using an 11.7 T magnet and a blood volume-weighted fMRI technique, we mapped the functional neuroanatomy of the mouse olfactory system. Consistent with reports on imaging of the much larger human brain, we mapped activity in regions of the olfactory bulb, as well as olfactory and limbic archicortex. By using two distinct odorants, we further demonstrated odorant-specific activation patterns. Our work thus provides a methodological framework for fMRI studies of olfactory dysfunction in mouse models of neurodegeneration.


Assuntos
Bulbo Olfatório/fisiologia , Condutos Olfatórios/fisiologia , Animais , Mapeamento Encefálico , Estudos de Viabilidade , Imagem por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Odorantes
2.
Methods Mol Biol ; 1718: 59-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29341002

RESUMO

Magnetic resonance imaging has been utilized as a quantitative and noninvasive method to image blood flow. Arterial spin labeling (ASL) is an MRI technique that images blood flow using arterial blood water as an endogenous tracer. Herein we describe the use of ASL to measure cerebral blood flow completely noninvasively in rodents, including methods, analysis, and important considerations when utilizing this technique.


Assuntos
Velocidade do Fluxo Sanguíneo , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , Imagem por Ressonância Magnética/métodos , Marcadores de Spin , Animais , Artérias Cerebrais/citologia , Camundongos
3.
J Glaucoma ; 26(5): 430-437, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28221328

RESUMO

PURPOSE: To investigate retinotopic functional representation in the visual cortex of mild to moderate primary open-angle glaucoma (POAG) participants and age-matched normal volunteers using high-resolution retinotopic blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). METHODS: fMRI was performed on 9 POAG participants (61±11 y old) and 9 age-matched controls (58±5 y old) were studied. A wide-view visual presentation (±55 degrees) was used to evaluate central and peripheral vision. Cortical magnification factors and BOLD% changes as a function of eccentricity. Correlation analysis between BOLD% changes and visual field scores, and between BOLD% changes and retinal nerve fiber layer thicknesses was performed. Comparison of BOLD% changes for individual visual field quadrants between POAG subgroups and normal group was performed. RESULTS: BOLD% changes of POAG participants in peripheral visual regions were reduced compared to normals but similar in central visual regions, consistent with the notion of peripheral vision being affected first and more compared to central vision. fMRI retinotopic mapping revealed enlarged representation of the parafovea in the visual cortex of POAG participants compared to normals. Cortical magnification of the central, but not peripheral, visual representation in the visual cortex was larger in POAG participants, suggesting functional remapping. BOLD% changes of individual visual field quadrants were significantly correlated with visual field scores and with retinal nerve fiber layer thickness in the corresponding quadrants. CONCLUSIONS: These results support the hypothesis that there are functional alteration and remapping in the topographic representation of the visual cortex in POAG participants, and these changes are correlated with disease severity.


Assuntos
Glaucoma de Ângulo Aberto/fisiopatologia , Plasticidade Neuronal/fisiologia , Nervo Óptico/diagnóstico por imagem , Retina/diagnóstico por imagem , Transtornos da Visão/diagnóstico , Córtex Visual/fisiologia , Adulto , Idoso , Feminino , Humanos , Pressão Intraocular/fisiologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Nervo Óptico/fisiopatologia , Retina/fisiopatologia , Campos Visuais/fisiologia
4.
J Glaucoma ; 26(2): 173-181, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27661989

RESUMO

PURPOSE OF THE STUDY: The purpose of the study was to evaluate neurodegeneration along brain visual pathways in primary open angle glaucoma (POAG) using improved analysis methods of volumetric and diffusion tensor magnetic resonance imaging (MRI) data. METHODS: Eleven POAG patients (60.0±9.2 y) with primarily mild to moderate POAG and 11 age-matched controls (55.9±7.5 y) were studied using structural and diffusion tensor MRI. Surface-based segmentation was applied to structural MRI to obtain visual cortical area and volume. Fiber tracking was applied to diffusion tensor data to obtain diffusion parameters along the optic tract and optic radiation. MRI parameters in glaucoma patients were compared with the corresponding left and right visual fields and retinal nerve fiber layer thicknesses, instead of with the left and right eye. RESULTS: Area and volume of the primary visual cortex were significantly reduced in POAG patients compared with controls (P<0.05) but did not correlate with visual field loss. Fractional anisotropy was reduced at multiple locations along the optic tracts and optic radiations in POAG patients compared with controls. Axial and radial diffusivity along the fiber tracts showed trends but were not significantly different between POAG patients and controls when averaged over the whole structures. Only fractional anisotropy (P<0.05) of the optic radiations was significantly correlated with visual field loss. No MRI parameters were correlated with retinal nerve fiber layer thickness. CONCLUSIONS: Improved analysis techniques of MRI data improves delineation of degeneration in the brain visual pathways and further supports the notion that neurodegeneration is involved with glaucoma pathogenesis.


Assuntos
Glaucoma de Ângulo Aberto/patologia , Imagem por Ressonância Magnética , Vias Visuais/patologia , Adulto , Idoso , Encéfalo , Imagem de Tensor de Difusão , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Campos Visuais
5.
NMR Biomed ; 29(7): 961-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27192391

RESUMO

Hyperbaric oxygen (HBO) therapy has a number of clinical applications. However, the effects of acute HBO on basal cerebral blood flow (CBF) and neurovascular coupling are not well understood. This study explored the use of arterial spin labeling MRI to evaluate changes in baseline and forepaw stimulus-evoked CBF responses in rats (n = 8) during normobaric air (NB), normobaric oxygen (NBO) (100% O2 ), 3 atm absolute (ATA) hyperbaric air (HB) and 3 ATA HBO conditions. T1 was also measured, and the effects of changes in T1 caused by increasing oxygen on the CBF calculation were investigated. The major findings were as follows: (i) increased inhaled oxygen concentrations led to a reduced respiration rate; (ii) increased dissolved paramagnetic oxygen had significant effects on blood and tissue T1 , which affected the CBF calculation using the arterial spin labeling method; (iii) the differences in blood T1 had a larger effect than the differences in tissue T1 on CBF calculation; (iv) if oxygen-induced changes in blood and tissue T1 were not taken into account, CBF was underestimated by 33% at 3 ATA HBO, 10% at NBO and <5% at HB; (v) with correction, CBF values under HBO, HB and NBO were similar (p > 0.05) and all were higher than CBF under NB by ~40% (p < 0.05), indicating that hypercapnia from the reduced respiration rate masks oxygen-induced vasoconstriction, although blood gas was not measured; and (vi) substantial stimulus-evoked CBF increases were detected under HBO, similar to NB, supporting the notion that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism. CBF MRI provides valuable insights into the effects of oxygen on basal CBF and neurovascular coupling under hyperbaric conditions. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Cerebrovascular/fisiologia , Oxigenação Hiperbárica/métodos , Angiografia por Ressonância Magnética/métodos , Oximetria/métodos , Oxigênio/metabolismo , Animais , Masculino , Oxigênio/sangue , Ratos , Ratos Sprague-Dawley
6.
Neuroimage ; 133: 498-503, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27033683

RESUMO

The brain depends on a continuous supply of oxygen to maintain its structural and functional integrity. This study measured T1 from MRI under normobaric air, normobaric oxygen, hyperbaric air, and hyperbaric oxygen (HBO) conditions as a marker of tissue pO2 since dissolved molecular oxygen acts as an endogenous contrast agent. Brain tissue T1 decreased corresponding to increased pO2 with increasing inhaled oxygen concentrations, and tissue oxygenation was estimated from the T1 changes between different inhaled oxygen levels. Tissue pO2 difference maps between different oxygen conditions showed heterogeneous pO2 changes in the brain. MRI-derived tissue pO2 was markedly lower than the arterial pO2 but was slightly higher than venous pO2. Additionally, for comparison with published extracellular tissue pO2 data obtained using oxygen electrodes and other invasive techniques, a model was used to estimate extracellular and intracellular pO2 from the MRI-derived mean tissue pO2. This required multiple assumptions, and so the effects of the assumptions and parameters used in modeling brain pO2 were evaluated. MRI-derived pO2 values were strongly dependent on assumptions about the extra- and intracellular compartments but were relatively less sensitive to variations in the relaxivity constant of oxygen and contribution from oxygen in the cerebral blood compartment. This approach may prove useful in evaluating tissue oxygenation in disease states such as stroke.


Assuntos
Encéfalo/metabolismo , Oxigenação Hiperbárica/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Oximetria/métodos , Oxigênio/sangue , Animais , Masculino , Imagem Molecular/métodos , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
PLoS One ; 11(3): e0151884, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27003179

RESUMO

The MitoPark mouse, a relatively new genetic model of Parkinson's disease (PD), has a dopaminergic neuron-specific knock-out that inactivates the mitochondrial transcription factor A (Tfam), a protein essential for mitochondrial DNA expression and maintenance. This study used multimodal MRI to characterize the neuroanatomical correlates of PD-related deficits in MitoPark mice, along with functional behavioral tests. Compared with age-matched wild-type animals, MitoPark mice at 30 weeks showed: i) reduced whole-brain volume and increased ventricular volume, indicative of brain atrophy, ii) reduced transverse relaxation time (T2*) of the substantia nigra and striatum, suggestive of abnormal iron accumulation, iii) reduced apparent diffusion coefficient in the substantia nigra, suggestive of neuronal loss, iv) reduced fractional anisotropy in the corpus callosum and substantia nigra, indicative of white-matter damages, v) cerebral blood flow was not significantly affected, and vi) reduced motor activity in open-field tests, reduced memory in novel object recognition tests, as well as decreased mobility in tail suspension tests, an indication of depression. In sum, MitoPark mice recapitulate changes in many MRI parameters reported in PD patients. Multimodal MRI may prove useful for evaluating neuroanatomical correlates of PD pathophysiology in MitoPark mice, and for longitudinally monitoring disease progression and therapeutic interventions for PD.


Assuntos
Corpo Estriado/patologia , Imagem por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Doença de Parkinson/fisiopatologia , Substância Negra/patologia , Testículo/fisiologia , Animais , Atrofia/genética , Atrofia/patologia , Comportamento Animal/fisiologia , DNA Mitocondrial/biossíntese , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Progressão da Doença , Feminino , Proteínas de Grupo de Alta Mobilidade/antagonistas & inibidores , Proteínas de Grupo de Alta Mobilidade/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/genética
8.
Invest Ophthalmol Vis Sci ; 57(3): 826-31, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26934140

RESUMO

PURPOSE: To test the hypothesis that acute topical dorzolamide (DZ) decreases intraocular pressure (IOP) and increases retinal and choroidal blood flow in the DBA/2J mouse model of glaucoma. METHODS: Retinal and choroidal blood flow were measured in 4- and 9-month-old DBA/2J mice, and 4-month C57BL/6 (control) mice under isoflurane anesthesia using magnetic resonance imaging. Ocular blood flow was measured at baseline, and 1 and 2 hours after topical dorzolamide. Intraocular pressure was measured using a rebound tonometer in a subset of animals at the same time points. RESULTS: Baseline IOP in the 4-month-old DBA/2J mice and C57BL/6 mice was not significantly different (P > 0.05), and IOP in both groups was less than in the 9-month-old DBA/2J mice (P < 0.05 for both). Compared to baseline, dorzolamide reduced IOP at 1 and 2 hours after dorzolamide in the 4- (P < 0.05) and 9-month-old (P < 0.01) DBA/2J mice, but not in the C57BL/6J mice (P > 0.05). Baseline retinal blood flow was lower in the 4-month and 9-month-old DBA/2J mice compared with the 4-month-old C57BL/6J mice (P < 0.05). Baseline choroidal blood flow in the 9-month-old DBA/2J mice was less than in the C57BL/6J mice (P < 0.05). Compared with baseline, both retinal and choroidal blood flow increased at 1-hour post-dorzolamide and remained elevated 2 hours later in the 9-month-old DBA/2J mice (P < 0.05). CONCLUSIONS: Dorzolamide lowers IOP and raises retinal and choroidal blood flow in older DBA/2J mice, consistent with the study hypothesis.


Assuntos
Corioide/irrigação sanguínea , Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Retina/fisiopatologia , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico , Animais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Corioide/efeitos dos fármacos , Corioide/patologia , Modelos Animais de Doenças , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Fluxo Sanguíneo Regional/fisiologia , Retina/efeitos dos fármacos , Retina/patologia , Resultado do Tratamento
9.
Radiology ; 279(1): 262-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26505923

RESUMO

PURPOSE: To apply resting-state functional magnetic resonance (MR) imaging to map functional connectivity of the human spinal cord. MATERIALS AND METHODS: Studies were performed in nine self-declared healthy volunteers with informed consent and institutional review board approval. Resting-state functional MR imaging was performed to map functional connectivity of the human cervical spinal cord from C1 to C4 at 1 × 1 × 3-mm resolution with a 3.0-T clinical MR imaging unit. Independent component analysis (ICA) was performed to derive resting-state functional MR imaging z-score maps rendered on two-dimensional and three-dimensional images. Seed-based analysis was performed for cross validation with ICA networks by using Pearson correlation. RESULTS: Reproducibility analysis of resting-state functional MR imaging maps from four repeated trials in a single participant yielded a mean z score of 6 ± 1 (P < .0001). The centroid coordinates across the four trials deviated by 2 in-plane voxels ± 2 mm (standard deviation) and up to one adjacent image section ± 3 mm. ICA of group resting-state functional MR imaging data revealed prominent functional connectivity patterns within the spinal cord gray matter. There were statistically significant (z score > 3, P < .001) bilateral, unilateral, and intersegmental correlations in the ventral horns, dorsal horns, and central spinal cord gray matter. Three-dimensional surface rendering provided visualization of these components along the length of the spinal cord. Seed-based analysis showed that many ICA components exhibited strong and significant (P < .05) correlations, corroborating the ICA results. Resting-state functional MR imaging connectivity networks are qualitatively consistent with known neuroanatomic and functional structures in the spinal cord. CONCLUSION: Resting-state functional MR imaging of the human cervical spinal cord with a 3.0-T clinical MR imaging unit and standard MR imaging protocols and hardware reveals prominent functional connectivity patterns within the spinal cord gray matter, consistent with known functional and anatomic layouts of the spinal cord.


Assuntos
Imagem por Ressonância Magnética/métodos , Medula Espinal/fisiologia , Adulto , Feminino , Voluntários Saudáveis , Humanos , Imagem Tridimensional , Masculino
10.
J Cereb Blood Flow Metab ; 36(6): 1135-42, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26661212

RESUMO

Reduced bioavailability of nitric oxide due to impaired endothelial nitric oxide synthase (eNOS) activity is a leading cause of endothelial dysfunction in diabetes. Enhancing eNOS activity in diabetes is a potential therapeutic target. This study investigated basal cerebral blood flow and cerebrovascular reactivity in wild-type mice, diabetic mice (Ins2(Akita+/-)), nondiabetic eNOS-overexpressing mice (TgeNOS), and the cross of two transgenic mice (TgeNOS-Ins2(Akita+/-)) at six months of age. The cross was aimed at improving eNOS expression in diabetic mice. The major findings were: (i) Body weights of Ins2(Akita+/-) and TgeNOS-Ins2(Akita+/-) were significantly different from wild-type and TgeNOS mice. Blood pressure of TgeNOS mice was lower than wild-type. (ii) Basal cerebral blood flow of the TgeNOS group was significantly higher than cerebral blood flow of the other three groups. (iii) The cerebrovascular reactivity in the Ins2(Akita+/-) mice was significantly lower compared with wild-type, whereas that in the TgeNOS-Ins2(Akita+/-) was significantly higher compared with the Ins2(Akita+/-) and TgeNOS groups. Overexpression of eNOS rescued cerebrovascular dysfunction in diabetic animals, resulting in improved cerebrovascular reactivity. These results underscore the possible role of eNOS in vascular dysfunction in the brain of diabetic mice and support the notion that enhancing eNOS activity in diabetes is a potential therapeutic target.


Assuntos
Circulação Cerebrovascular/genética , Transtornos Cerebrovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Óxido Nítrico Sintase Tipo III/genética , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Transtornos Cerebrovasculares/genética , Diabetes Mellitus Experimental , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Expressão Gênica , Camundongos , Camundongos Transgênicos , Terapia de Alvo Molecular/métodos
11.
Neuroimage ; 119: 382-9, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26143203

RESUMO

Hyperbaric oxygen (HBO) therapy is used to treat a number of ailments. Improved understanding of how HBO affects neuronal activity, cerebral blood flow (CBF) and blood-oxygenation-level dependent (BOLD) changes could shed light on the role of oxygen in neurovascular coupling and help guide HBO treatments. The goal of this study was to test two hypotheses: i) activation-induced CBF fMRI response is not dependent on hemoglobin deoxygenation, and ii) activation-induced BOLD fMRI is markedly attenuated under HBO. CBF and BOLD fMRI of forepaw stimulation in anesthetized rats under HBO at 3 atmospheres absolute (ATA) were compared with normobaric air. Robust BOLD and CBF fMRI were detected under HBO. Inflow effects and spin-density changes did not contribute significantly to the BOLD fMRI signal under HBO. Analysis of the T2(⁎)-weighted signal at normobaric air and 1, 2 and 3ATA oxygen in the tissue and the superior sagittal sinus showed a strong dependence on increasing inhaled [O2]. Spontaneous electrophysiological activity and evoked local-field potentials were reduced under HBO. The differences between normobaric air and HBO in basal and evoked electrical activity could not fully account for the strong BOLD responses under HBO. We concluded that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism and that stimulus-evoked BOLD responses and the venous T2(⁎)-weighted signals still have room to increase under 3ATA HBO. To our knowledge, this is the first fMRI study under HBO, providing insights into the effects of HBO on neural activity, neurovascular coupling, tissue oxygenation, and the BOLD signal.


Assuntos
Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Imagem por Ressonância Magnética , Acoplamento Neurovascular , Oxigênio/metabolismo , Pressão do Ar , Animais , Estimulação Elétrica , Frequência Cardíaca , Hemodinâmica , Hemoglobinas/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Taxa Respiratória , Córtex Somatossensorial/irrigação sanguínea , Córtex Somatossensorial/fisiologia , Percepção do Tato/fisiologia
12.
J Cereb Blood Flow Metab ; 35(11): 1852-61, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26104285

RESUMO

This study investigated the effects of perturbed cerebral blood flow (CBF) and cerebrovascular reactivity (CR) on relaxation time constant (T2), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and behavioral scores at 1 and 3 hours, 2, 7, and 14 days after traumatic brain injury (TBI) in rats. Open-skull TBI was induced over the left primary forelimb somatosensory cortex (N=8 and 3 sham). We found the abnormal areas of CBF and CR on days 0 and 2 were larger than those of the T2, ADC, and FA abnormalities. In the impact core, CBF was reduced on day 0, increased to 2.5 times of normal on day 2, and returned toward normal by day 14, whereas in the tissue surrounding the impact, hypoperfusion was observed on days 0 and 2. CR in the impact core was negative, most severe on day 2 but gradually returned toward normal. T2, ADC, and FA abnormalities in the impact core were detected on day 0, peaked on day 2, and pseudonormalized by day 14. Lesion volumes peaked on day 2 and were temporally correlated with forelimb asymmetry and foot-fault scores. This study quantified the effects of perturbed CBF and CR on structural magnetic resonance imaging and behavioral readouts.


Assuntos
Comportamento Animal , Lesões Encefálicas/patologia , Lesões Encefálicas/psicologia , Circulação Cerebrovascular , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/psicologia , Animais , Imagem de Tensor de Difusão , Vias Eferentes/patologia , Membro Anterior/inervação , Hipercapnia/patologia , Hipercapnia/psicologia , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/patologia
13.
Invest Ophthalmol Vis Sci ; 56(6): 4006-12, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26098468

RESUMO

PURPOSE: To employ high-resolution manganese-enhanced MRI (MEMRI) to study abnormal calcium activity in different cell layers in streptozotocin-induced diabetic rat retinas, and to determine whether MEMRI detects changes at earlier time points than previously reported. METHODS: Sprague-Dawley rats were studied 14 days (n = 8) and 30 days (n = 5) after streptozotocin (STZ) or vehicle (n = 7) injection. Manganese-enhanced MRI at 20 × 20 × 700 µm, in which contrast is based on manganese as a calcium analogue and an MRI contrast agent, was obtained in light and dark adaptation of the retina in the same animals in which one eye was covered and the fellow eye was not. The MEMRI activity encoding of the light and dark adaptation was achieved in awake conditions and imaged under anesthesia. RESULTS: Manganese-enhanced MRI showed three layers, corresponding to the inner retina, outer retina, and the choroid. In normal animals, the outer retina showed higher MEMRI activity in dark compared to light; the inner retina displayed lower activity in dark compared to light; and the choroid showed no difference in activity. Manganese-enhanced MRI activity changed as early as 14 days after hyperglycemia and decreased with duration of hyperglycemia in the outer retina in dark relative to light adaptation. The choroid also had altered MEMRI activity at 14 days, which returned to normal by 30 days. No differences in MEMRI activity were detected in the inner retina. CONCLUSIONS: Manganese-enhanced MRI detects progressive reduction in calcium activity with duration of hyperglycemia in the outer retina as early as 14 days after hyperglycemia, earlier than any other time point reported in the literature.


Assuntos
Adaptação Ocular/fisiologia , Meios de Contraste , Adaptação à Escuridão/fisiologia , Imagem por Ressonância Magnética/métodos , Compostos de Manganês , Retina/fisiologia , Animais , Diabetes Mellitus Experimental , Masculino , Ratos , Ratos Sprague-Dawley
14.
Neuroimage ; 111: 329-37, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25731987

RESUMO

Chronic hypertension alters cerebral vascular morphology, cerebral blood flow (CBF), cerebrovascular reactivity, and increses susceptibility to neurological disorders. This study evaluated: i) the lumen diameters of major cerebral and downstream arteries using magnetic resonance angiography, ii) basal CBF, and iii) cerebrovascular reactivity to hypercapnia of multiple brain regions using arterial-spin-labeling technique in spontaneously hypertensive rats (SHR) at different stages. Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In 10-week SHR, lumen diameter started to reduce, basal CBF, and hypercapnic CBF response were higher from elevated arterial blood pressure, but there was no evidence of stenosis, compared to age-matched WKY. In 20-week SHR, lumen diameter remained reduced, CBF returned toward normal from vasoconstriction, hypercapnic CBF response reversed and became smaller, but without apparent stenosis. In 40-week SHR, lumen diameter remained reduced and basal CBF further decreased, resulting in larger differences compared to WKY. There was significant stenosis in main supplying cerebral vessels. Hypercapnic CBF response further decreased, with some animals showing negative hypercapnic CBF responses in some brain regions, indicative of compromised cerebrovascular reserve. The territory with negative hypercapnia CBF responses corresponded with the severity of stenosis in arteries that supplied those territories. We also found enlargement of downstream vessels and formation of collateral vessels as compensatory responses to stenosis of upstream vessels. The middle cerebral and azygos arteries were amongst the most susceptible to hypertension-induced changes. Multimodal MRI provides clinically relevant data that might be useful to characterize disease pathogenesis, stage disease progression, and monitor treatment effects in hypertension.


Assuntos
Doenças Arteriais Cerebrais/fisiopatologia , Circulação Cerebrovascular/fisiologia , Hipercapnia/fisiopatologia , Hipertensão/fisiopatologia , Animais , Angiografia Cerebral , Doenças Arteriais Cerebrais/patologia , Constrição Patológica , Modelos Animais de Doenças , Hipercapnia/patologia , Hipertensão/patologia , Angiografia por Ressonância Magnética , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Marcadores de Spin
15.
Curr Eye Res ; 39(10): 1059-67, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24655028

RESUMO

PURPOSE: To verify that a visual fixation protocol with cued eye blinks achieves sufficient stability for magnetic resonance imaging (MRI) blood-flow measurements and to determine if choroidal blood flow (ChBF) changes with age in humans. METHODS: The visual fixation stability achievable during an MRI scan was measured in five normal subjects using an eye-tracking camera outside the MRI scanner. Subjects were instructed to blink immediately after recorded MRI sound cues but to otherwise maintain stable visual fixation on a small target. Using this fixation protocol, ChBF was measured with MRI using a 3 Tesla clinical scanner in 17 normal subjects (24-68 years old). Arterial and intraocular pressures (IOP) were measured to calculate perfusion pressure in the same subjects. RESULTS: The mean temporal fluctuations (standard deviation) of the horizontal and vertical displacements were 29 ± 9 µm and 38 ± 11 µm within individual fixation periods, and 50 ± 34 µm and 48 ± 19 µm across different fixation periods. The absolute displacements were 67 ± 31 µm and 81 ± 26 µm. ChBF was negatively correlated with age (R = -0.7, p = 0.003), declining 2.7 ml/100 ml/min per year. There were no significant correlations between ChBF versus perfusion pressure, arterial pressure, or IOP. There were also no significant correlations between age versus perfusion pressure, arterial pressure, or IOP. Multiple regression analysis indicated that age was the only measured independent variable that was significantly correlated with ChBF (p = 0.03). CONCLUSIONS: The visual fixation protocol with cued eye blinks was effective in achieving sufficient stability for MRI measurements. ChBF had a significant negative correlation with age.


Assuntos
Envelhecimento/fisiologia , Corioide/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Feminino , Fixação Ocular/fisiologia , Humanos , Pressão Intraocular/fisiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Methods Mol Biol ; 1135: 205-11, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24510866

RESUMO

Magnetic resonance imaging can be utilized as a quantitative and noninvasive method to image cerebral blood flow. The two most common techniques used to detect cerebral blood flow are dynamic susceptibility contrast (DSC) perfusion MRI and arterial spin labeling perfusion MRI. Herein we describe the use of these two techniques to measure cerebral blood flow in rodents, including methods, analysis, and important considerations when utilizing these techniques.


Assuntos
Circulação Cerebrovascular , Angiografia por Ressonância Magnética , Animais , Meios de Contraste , Gadolínio DTPA , Ratos , Fluxo Sanguíneo Regional , Marcadores de Spin
17.
Magn Reson Med ; 72(4): 1176-81, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24243603

RESUMO

PURPOSE: Hyperbaric oxygen therapy has shown efficacies in the treatment of a number of diseases. The goal of this study was to develop a rodent hyperbaric chamber for MRI studies and to investigate the effects of hyperbaric air and hyperbaric oxygen on local magnetic field (B0 ) and MRI relaxation parameters in the rat brain. METHODS: A hyperbaric chamber, constructed to fit inside an animal MRI scanner, was pressurized with air to four atmospheres, while oxygen was delivered locally via nose cone. B0 , T2 , T2 *, and T1 maps in the rat brain were evaluated under normobaric air, hyperbaric air, and hyperbaric oxygen at 7T. RESULTS: Under hyperbaric oxygen, images exhibited artifacts and temporal instability, attributable to fluctuating oxygen concentration from air and oxygen mixing near the imaging region. Physically shielding the imaging region from fluctuating oxygen concentration resolved the problems. With increasing oxygen at hyperbaric pressure, B0 was shifted downfield with increased inhomogeneity near the ear canals and nose. Brain T2 and T2 * were lengthened, and T1 was shortened. CONCLUSION: This study establishes the means to perform MRI on rodents under hyperbaric conditions. Hyperbaric air and hyperbaric oxygen have significant effects on B0 and tissue relaxation parameters compared with normobaric air.


Assuntos
Ar , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Oxigenação Hiperbárica/métodos , Imagem por Ressonância Magnética/métodos , Oxigênio/farmacologia , Respiração com Pressão Positiva/métodos , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Oxigenação Hiperbárica/instrumentação , Interpretação de Imagem Assistida por Computador/métodos , Campos Magnéticos , Imagem por Ressonância Magnética/instrumentação , Masculino , Respiração com Pressão Positiva/instrumentação , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Magn Reson Med ; 69(1): 221-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22392583

RESUMO

This study tested the sensitivity of an arterial spin labeling MRI method to image changes in retinal and choroidal blood flow (BF) and anatomical thickness of the retina in the rd10 mouse model of retinitis pigmentosa. High-resolution (42 × 42 µm) MRI was performed on rd10 mice and age-matched controls at 25, 35, and 60 days of age (n = 6 each group) on a 7-T scanner. Anatomical MRI was acquired, and quantitative BF was imaged using arterial spin labeling MRI with a separate cardiac labeling coil. Histology was obtained to confirm thickness changes in the retina. In control mice, the retinal and choroidal vascular layers were quantitatively resolved. In rd10 mice, retinal BF decreased progressively over time, while choroidal BF was unchanged. The rd10 retina became progressively thinner at later time points compared with age-matched controls by anatomical MRI and histology (P < 0.01). BF and anatomical MRI were capable of detecting decreased BF and thickness in the rd10 mouse retina. Because BF is tightly coupled to metabolic function, BF MRI has the potential to noninvasively assess retinal diseases in which metabolism and function are perturbed and to evaluate novel treatments, complementing existing retinal imaging techniques.


Assuntos
Corioide/irrigação sanguínea , Imagem por Ressonância Magnética , Artéria Retiniana/fisiologia , Retinite Pigmentosa/fisiopatologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fluxo Sanguíneo Regional , Retina/patologia , Retinite Pigmentosa/patologia , Marcadores de Spin
19.
Radiology ; 266(3): 905-11, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23220896

RESUMO

PURPOSE: To develop a magnetic resonance (MR) imaging approach to noninvasively image quantitative Po(2) in the human vitreous. MATERIALS AND METHODS: Human studies were approved by the institutional review board with informed consent obtained from all subjects and were HIPAA compliant. Animal studies were performed with animal care committee approval. An MR imaging method to measure the longitudinal relaxation rate, or R1, of water was implemented with a 3.0-T MR imager. R1 was calibrated in water phantoms at multiple Po(2) and temperature conditions (n = 10) and in ex vivo animal vitreous (n = 2). Vitreous Po(2) was imaged in three human volunteers (age range, 26-28 years) in multiple sessions on separate days to evaluate reproducibility. The effects of temperature and ambient air were evaluated by acquiring data with the eye open and closed. Statistical analysis consisted of t tests, with P less than .05 indicating significant difference. RESULTS: Calibrations of phantoms and ex vivo vitreous yielded an R1 association with oxygen of 0.209 sec(-1) + Po(2) ⋅ 2.07 × 10(-4) sec(-1)/mm Hg at 37°C, and an association with temperature (Δ[1/R1]/ΔTemperature) of 0.106 sec/°C ± 0.009 (standard deviation). A difference in R1 was found between the phantoms and vitreous. If uncorrected, vitreal Po(2) would be significantly overestimated (P < .001). In vivo human vitreous Po(2) maps were spatially heterogeneous, with a whole vitreous Po(2) of 16.7 mm Hg ± 6.5 (eye closed). Measurements between open and closed eyes showed spatially dependent R1 differences, which translated to temperature differences of 0.34°-0.83°C across the eye. CONCLUSION: This study established an MR imaging protocol to image quantitative vitreous Po(2) noninvasively and evaluated effects from vitreal macromolecules, temperature gradients, and ambient air on vitreal Po(2) values. Measurement of vitreous Po(2) with MR imaging has the potential to be used to study eye diseases noninvasively.


Assuntos
Imagem por Ressonância Magnética/métodos , Oximetria/métodos , Oxigênio/análise , Corpo Vítreo/química , Corpo Vítreo/citologia , Adulto , Animais , Feminino , Humanos , Masculino , Coelhos
20.
Invest Ophthalmol Vis Sci ; 53(10): 6488-94, 2012 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-22915034

RESUMO

PURPOSE: To investigate ocular blood flow and visual function in the Ins2(Akita) diabetic retinopathy mouse model at early and late time points after onset of hyperglycemia. METHODS: Mice heterozygous for the Ins2(Akita) mutation, which become hyperglycemic at approximately 4 weeks old, were studied at 2.5 and 7.5 months of age, with age-matched wild-type littermates used as controls. Retinal and choroidal blood flows were noninvasively imaged at 42 × 42 × 400 µm using magnetic resonance imaging. Visual function was measured using optokinetic tracking to determine spatial frequency and contrast thresholds from the same mice. RESULTS: At 2.5 months, choroidal blood flow was significantly reduced (P < 0.01) by 20% in Ins2(Akita) mice (n = 13) compared with age-matched controls (n = 16), whereas retinal blood flow and visual function were not significantly affected (P > 0.05). At 7.5 months, both choroidal and retinal blood flow were significantly reduced (P < 0.05) by 27% and 28%, respectively, in Ins2(Akita) mice (n = 11) compared with age-matched controls (n = 15). Visual functions were also significantly worse (P < 0.05) in Ins2(Akita) mice at 7.5 months, as indicated by a 19% decreased spatial frequency threshold and 135% increased contrast threshold compared with age-matched controls. The magnitudes of the blood flow and vision deficits, however, were not correlated. CONCLUSIONS: Although both choroidal and retinal blood flow and vision were altered after prolonged diabetes in the Ins2(Akita) mouse, choroidal blood flow was reduced even in young diabetic animals, suggesting ocular blood flow deficit could be an early pathological change in diabetic retinopathy.


Assuntos
Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Vasos Retinianos/fisiopatologia , Animais , Corioide/irrigação sanguínea , Corioide/fisiologia , Sensibilidades de Contraste/fisiologia , Retinopatia Diabética/genética , Modelos Animais de Doenças , Diagnóstico Precoce , Feminino , Hiperglicemia/genética , Hiperglicemia/fisiopatologia , Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Estimulação Luminosa/métodos , Retina/patologia , Retina/fisiopatologia , Vasos Retinianos/patologia , Limiar Sensorial/fisiologia
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