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.
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Encéfalo/metabolismo , Oxigenoterapia Hiperbárica/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Oximetria/métodos , Oxigênio/sangue , Animais , Masculino , Imagem Molecular/métodos , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
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
Imageamento por Ressonância Magnética/métodos , Medula Espinal/fisiologia , Adulto , Feminino , Voluntários Saudáveis , Humanos , Imageamento Tridimensional , MasculinoRESUMO
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 , Oxigenoterapia Hiperbárica/métodos , Angiografia por Ressonância Magnética/métodos , Oximetria/métodos , Oxigênio/metabolismo , Animais , Masculino , Oxigênio/sangue , Ratos , Ratos Sprague-DawleyRESUMO
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.
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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 SpinRESUMO
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(â)-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(â)-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 , Imageamento 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/fisiologiaRESUMO
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 , Oxigenoterapia Hiperbárica/métodos , Imageamento por Ressonância Magnética/métodos , Oxigênio/farmacologia , Respiração com Pressão Positiva/métodos , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Oxigenoterapia Hiperbárica/instrumentação , Interpretação de Imagem Assistida por Computador/métodos , Campos Magnéticos , Imageamento por Ressonância Magnética/instrumentação , Masculino , Respiração com Pressão Positiva/instrumentação , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Purpose: The purpose of this study was to utilize multi-parametric magnetic resonance imaging (MRI) to investigate in vivo age-related changes in the physiology and optics of mouse lenses where Connexin 50 has been deleted (Cx50KO) or replaced by Connexin 46 (Cx50KI46). Methods: The lenses of transgenic Cx50KO and Cx50KI46 mice were imaged between 3 weeks and 6 months of age using a 7T MRI. Measurements of lens geometry, the T2 (water-bound protein ratios), the refractive index (n), and T1 (free water content) values were calculated by processing the acquired images. The lens power was calculated from an optical model that combined the geometry and the n. All transgenic mice were compared with control mice at the same age. Results: Cx50KO and Cx50KI46 mice developed smaller lenses compared with control mice. The lens thickness, volume, and surface radii of curvatures all increased with age but were limited to the size of the lenses. Cx50KO lenses exhibited higher lens power than Cx50KI46 lenses at all ages, and this was correlated with significantly lower water content in these lenses, which was probably modulated by the gap junction coupling. The refractive power tended to a steady state with age, similar to the control mice. Conclusions: The modification of Cx50 gap junctions significantly impacted lens growth and physiological optics as the mouse aged. The lenses showed delayed development growth, and altered optics governed by different lens physiology. This research provides new insights into how gap junctions regulate the development of the lens's physiological optics.
Assuntos
Conexinas , Cristalino , Camundongos Transgênicos , Animais , Cristalino/metabolismo , Conexinas/metabolismo , Conexinas/genética , Camundongos , Imageamento por Ressonância Magnética , Envelhecimento/fisiologia , Refração Ocular/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Junções Comunicantes/fisiologia , Junções Comunicantes/metabolismoRESUMO
Purpose: Blood flow (BF) of the retinal and choroidal vasculatures can be quantitatively imaged using MRI. This study sought to improve methods of data acquisition and analysis for MRI of layer-specific retinal and choroidal BF and then applied this approach to detect reduced ocular BF in a well-established mouse model of glaucoma from both eyes. Methods: Quantitative BF magnetic resonance imaging (MRI) was performed on glaucomatous DBA/2J and normal C57BL/6J mice. Arterial spin labeling MRI was applied to image retinal and choroidal BF using custom-made dual eye coils that could image both eyes during the same scan. Statistics using data from a single eye or two eyes were compared. BF values were calculated using two approaches. The BF rate per quantity of tissue was calculated as commonly done, and the peak BF values of the retinal and choroidal vasculatures were taken. Additionally, the BF rate per retinal surface area was calculated using a new analysis approach to attempt to reduce partial volume and variability by integrating BF over the retinal and choroidal depths. Results: Ocular BF of both eyes could be imaged using the dual coil setup without effecting scan time. Intraocular pressure was significantly elevated in DBA/2J mice compared to C57BL/6J mice (P<0.01). Both retinal and choroidal BF were significantly decreased in DBA/2J mice in comparison to the age-matched normal C57BL/6J mice across all measurements (P < 0.01). From simulations, the values from the integrated BF analysis method had less partial volume effect, and from in vivo scans, this analysis approach also improved power. Conclusion: The dual eye coil setup allows bilateral eye data acquisition, increasing the amount of data acquired without increasing acquisition times in vivo. The reduced ocular BF found using the improved acquisition and analysis approaches replicated the results of previous studies on DBA/2J mice. The ocular hypertensive stress-induced BF reduction found within these mice may represent changes associated with glaucomatous progression.
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) â 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
Imageamento por Ressonância Magnética/métodos , Oximetria/métodos , Oxigênio/análise , Corpo Vítreo/química , Corpo Vítreo/citologia , Adulto , Animais , Feminino , Humanos , Masculino , CoelhosRESUMO
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 , Imageamento por Ressonância Magnética , Artéria Retiniana/fisiologia , Retinose Pigmentar/fisiopatologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fluxo Sanguíneo Regional , Retina/patologia , Retinose Pigmentar/patologia , Marcadores de SpinRESUMO
Abnormal intraocular fluid flow or clearance is involved with a variety of eye diseases such as glaucoma and diabetic retinopathy, but measurement of water exchange dynamics in the vitreous and aqueous remain challenging. 2H MRI can be used to image deuterium oxide (D2O) as a tracer, but the signal-to-noise ratio for deuterium is low due to its low concentration, which has hampered its application to imaging the eye. To overcome this challenge, we investigated the feasibility of direct D2O MRI to measure water dynamics in the mouse eye. The balanced steady-state free precession (bSSFP) sequence provided substantially higher signal-to-noise ratio for imaging D2O in fluid compared to standard gradient echo and spin echo sequences. bSSFP allowed dynamic imaging of intraocular water inflow in the mouse with 41 s temporal resolution. The inflow rate in the vitreous was found to be faster than in the aqueous. These studies demonstrate the feasibility of in vivo imaging of water inflow dynamics into the both the vitreous and aqueous in mice, which could be useful in studies of abnormal fluid exchange in rodent models of eye disease.
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Glaucoma , Água , Camundongos , Animais , Óxido de Deutério , Imageamento por Ressonância Magnética/métodos , Razão Sinal-RuídoRESUMO
High-resolution retinotopic blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) with a wide-view presentation can be used to functionally map the peripheral and central visual cortex. This method for measuring functional changes of the visual brain allows for functional mapping of the occipital lobe, stimulating >100° (±50°) or more of the visual field, compared to standard fMRI visual presentation setups which usually cover <30° of the visual field. A simple wide-view stimulation system for BOLD fMRI can be set up using common MR-compatible projectors by placing a large mirror or screen close to the subject's face and using only the posterior half of a standard head coil to provide a wide-viewing angle without obstructing their vision. The wide-view retinotopic fMRI map can then be imaged using various retinotopic stimulation paradigms, and the data can be analyzed to determine the functional activity of visual cortical regions corresponding to central and peripheral vision. This method provides a practical, easy-to-implement visual presentation system that can be used to evaluate changes in the peripheral and central visual cortex due to eye diseases such as glaucoma and the vision loss that may accompany them.
Assuntos
Imageamento por Ressonância Magnética , Córtex Visual , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Córtex Visual/fisiologia , Campos Visuais , Percepção Visual/fisiologia , Estimulação Luminosa/métodos , Vias VisuaisRESUMO
Purpose: The purpose of this study was to utilize in vivo magnetic resonance imaging (MRI) and optical modeling to investigate how changes in water transport, lens curvature, and gradient refractive index (GRIN) alter the power of the mouse lens as a function of age. Methods: Lenses of male C57BL/6 wild-type mice aged between 3 weeks and 12 months (N = 4 mice per age group) were imaged using a 7T MRI scanner. Measurements of lens shape and the distribution of T2 (water-bound protein ratios) and T1 (free water content) values were extracted from MRI images. T2 values were converted into the refractive index (n) using an age-corrected calibration equation to calculate the GRIN at different ages. GRIN maps and shape parameters were inputted into an optical model to determine ageing effects on lens power and spherical aberration. Results: The mouse lens showed two growth phases. From 3 weeks to 3 months, T2 decreased, GRIN increased, and T1 decreased. This was accompanied by increased lens thickness, volume, and surface radii of curvatures. The refractive power of the lens also increased significantly, and a negative spherical aberration was developed and maintained. Between 6 and 12 months of age, all physiological, geometrical, and optical parameters remained constant, although the lens continued to grow. Conclusions: In the first 3 months, the mouse lens power increased as a result of changes in shape and in the GRIN, the latter driven by the decreased water content of the lens nucleus. Further research into the mechanisms regulating this decrease in mouse lens water could improve our understanding of how lens power changes during emmetropization in the developing human lens.
Assuntos
Cristalino , Refração Ocular , Masculino , Humanos , Animais , Camundongos , Recém-Nascido , Tomografia de Coerência Óptica/métodos , Camundongos Endogâmicos C57BL , Cristalino/fisiologia , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: To develop high-spatial-resolution magnetic resonance (MR) microangiography techniques to image the rat ocular circulation. MATERIALS AND METHODS: Animal experiments were performed with institutional Animal Care Committee approval. MR microangiography (resolution, 84×84×84 µm or 42×42×84 µm) of the rat eye (eight rats) was performed by using a custom-made small circular surface coil with an 11.7-T MR unit before and after monocrystalline iron oxide nanoparticle (MION) injection. MR microangiography measurements were made during air, oxygen, and carbogen inhalation. From three-dimensional MR microangiography, the retina was virtually flattened to enable en face views of various retinal depths, including the retinal and choroidal vascular layers. Signal intensity changes within the retinal or choroidal arteries and veins associated with gas challenges were analyzed. Statistical analysis was performed by using paired t tests, with P<.05 considered to indicate a significant difference. Bonferroni correction was used to adjust for multiple comparisons. RESULTS: The central retinal artery, long posterior ciliary arteries, and choroidal vasculature could be distinguished on MR microangiograms of the eye. With MR microangiography, retinal arteries and veins could be distinguished on the basis of blood oxygen level-dependent contrast. Carbogen inhalation-enhanced MR microangiography signal intensity in both the retina (P=.001) and choroid (P=.027) compared with oxygen inhalation. Carbogen inhalation showed significantly higher signal intensity changes in the retinal arteries (P=.001, compared with oxygen inhalation), but not in the veins (P=.549). With MION administration, MR microangiography depicted retinal arterial vasoconstriction when the animals were breathing oxygen (P=.02, compared with animals breathing air). CONCLUSION: MR microangiography of the eye allows depth-resolved imaging of small angiographic details of the ocular circulation. This approach may prove useful in studying microvascular pathologic findings and neurovascular dysfunction in the eye and retina.
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Oftalmopatias/diagnóstico , Olho/irrigação sanguínea , Angiografia por Ressonância Magnética/métodos , Neovascularização Patológica/patologia , Animais , Meios de Contraste/administração & dosagem , Dextranos/administração & dosagem , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Angiografia por Ressonância Magnética/instrumentação , Nanopartículas de Magnetita/administração & dosagem , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
3D-MR microscopy at 11.7T and 20 × 20 × 57 µm resolution was performed on formalin-fixed rat eyes with: (I) no contrast agent and (II) Gadodiamide (Omniscan(®) ) added to the fixative. Group I data showed generally poor contrast among layers. Group II data showed markedly better lamina-specific contrast with the nerve fiber + ganglion cell layer and inner nuclear layer being hypointense, and the inner plexiform, outer plexiform, outer nuclear layer, and the segments being hyperintense. The signal-to-noise ratio in group II was higher than group I, consistent with Gadodiamide acting as a T(1) -contrast agent. All major retinal layers were assigned and their thicknesses quantified with corroboration by histology. MR microscopy allows nondestructive examination of valuable specimens and could have applications in disease and in vivo.
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Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Retina/anatomia & histologia , Animais , Meios de Contraste/administração & dosagem , Gadolínio DTPA/administração & dosagem , Técnicas In Vitro , Ratos , Ratos Sprague-Dawley , Razão Sinal-RuídoRESUMO
Nitroprusside, a vasodilatory nitric oxide donor, is clinically used during vascular surgery and to lower blood pressure in acute hypertension. This article reports a novel application of blood flow (BF) and blood oxygenation level dependent (BOLD) MRI on an 11.7T scanner to image the rat chorioretinal BF and BOLD changes associated with graded nitroprusside infusion. At low doses (1 or 2 µg/kg/min), nitroprusside increased BF as expected but decreased BOLD signals, showing an intriguing BF-BOLD uncoupling. At high doses (3-5 µg/kg/min), nitroprusside decreased BF and markedly decreased BOLD signals. To our knowledge, this is the first pharmacological MRI application of the retina. This approach has potential to open up new avenues to study the drug-related hemodynamic functions and to evaluate the effects of novel therapeutic interventions on BOLD and BF in the normal and diseased retinas.
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Corioide/efeitos dos fármacos , Corioide/fisiologia , Imageamento por Ressonância Magnética/métodos , Nitroprussiato/administração & dosagem , Oxigênio/sangue , Retina/efeitos dos fármacos , Retina/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Infusões Intra-Arteriais , Masculino , Ratos , Ratos Long-Evans , Vasodilatadores/administração & dosagemRESUMO
The Royal College of Surgeons (RCS) rat is an established animal model of retinitis pigmentosa, a family of inherited retinal diseases which starts with loss of peripheral vision and progresses to eventual blindness. Blood flow (BF), an important physiological parameter, is intricately coupled to metabolic function under normal physiological conditions and is perturbed in many neurological and retinal diseases. This study reports non-invasive high-resolution MRI (44 × 44 × 600 µm) to image quantitative retinal and choroidal BF and layer-specific retinal thicknesses in RCS rat retinas at different stages of retinal degeneration compared with age-matched controls. The unique ability to separate retinal and choroidal BF was made possible by the depth-resolved MRI technique. RBF decreased with progressive retinal degeneration, but ChBF did not change in RCS rats up to post-natal day 90. We concluded that choroidal and retinal circulations have different susceptibility to progressive retinal degeneration in RCS rats. Layer-specific retinal thickness became progressively thinner and was corroborated by histological analysis in the same animals. MRI can detect progressive anatomical and BF changes during retinal degeneration with laminar resolution.
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Corioide/irrigação sanguínea , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Vasos Retinianos/fisiologia , Retinose Pigmentar/fisiopatologia , Animais , Velocidade do Fluxo Sanguíneo , Ratos , Ratos Long-Evans , Ratos Mutantes , Fluxo Sanguíneo RegionalRESUMO
PURPOSE: To test the hypothesis that mild chronic hyperoxia treatment would improve retinal function despite a progressive decline in ocular blood flow in the DBA/2J mouse model of glaucoma. MATERIALS AND METHODS: DBA/2J mice were treated with chronic mild hyperoxia (30% O2) beginning at 4.5 months of age or were untreated by giving normal room air. Retinal and choroidal blood flow (RBF and ChBF, respectively) were measured at 4, 6, and 9 months of age by MRI. Blood flow was additionally measured under hypercapnia challenge (5% CO2 inhalation) to assess vascular reactivity. Intraocular pressure (IOP) was measured using a rebound tonometer at the same time points. Scotopic flash electroretinograms (ERGs) were recorded at 9 months of age. RESULTS: Both ChBF and RBF were reduced and significantly affected by age (p < 0.01), but neither were significantly affected by O2-treatment (p > 0.05). ChBF significantly increased in response to hypercapnia (p < 0.01), which was also unaffected by O2-treatment. Significant effects of age (p < 0.001) and of the interaction of age with treatment (p = 0.028) were found on IOP. IOP significantly decreased in O2-treated mice at 6 months compared to 4 months of age (p < 0.001), while IOP trended to increase with age in untreated mice. The amplitude of the b-wave from ERG was significantly increased in O2-treated DBA/2J compared to the untreated mice (p = 0.012), while the a-wave and oscillatory potentials were not significantly affected (p > 0.05). CONCLUSION: This study investigated the effects of chronic mild hyperoxia on retinal function and on retinal and choroidal blood flow in a mouse model of glaucoma. Retinal function was improved in the O2-treated mice at late stage, despite a progressive decline of RBF and ChBF with age that was comparable to untreated mice.
Assuntos
Glaucoma , Hiperóxia , Animais , Modelos Animais de Doenças , Hipercapnia , Pressão Intraocular , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBARESUMO
The retina consists of multiple cellular and synaptic layers and is nourished by two distinct (retinal and choroidal) circulations bounding the retina, separated by an avascular layer. High spatiotemporal resolution, layer-specific MRI of the retina remains challenging due to magnetic inhomogeneity-induced artifacts. This study reports passband balanced steady-state free-precession (bSSFP) MRI at 45×45×500 µm and 1.6 s temporal resolution to image the mouse retina, overcoming geometric distortion and signal dropout while maintaining rapid acquisition and high signal-to-noise ratio. bSSFP images revealed multiple alternating dark-bright-dark-bright retinal layers. Hypoxic (10% O(2) ) inhalation decreased bSSFP signals in the two layers bounding the retina, corresponding to the retinal and choroidal vasculatures. The layer in between showed no substantial response and was assigned the avascular photoreceptor layers. Choroidal responses (-25.9 ± 6.4%, mean ± SD, n=6) were significantly (P<0.05) larger than retinal vascular responses (-11.6±2.4%). bSSFP offers very high spatiotemporal resolution and could have important applications in imaging layer-specific changes in retinal diseases.