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2.
Am J Physiol Endocrinol Metab ; 307(9): E773-83, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25159329

RESUMO

The steroid receptor coactivator 1 (SRC1) regulates key metabolic pathways, including glucose homeostasis. SRC1(-/-) mice have decreased hepatic expression of gluconeogenic enzymes and a reduction in the rate of endogenous glucose production (EGP). We sought to determine whether decreasing hepatic and adipose SRC1 expression in normal adult rats would alter glucose homeostasis and insulin action. Regular chow-fed and high-fat-fed male Sprage-Dawley rats were treated with an antisense oligonucleotide (ASO) against SRC1 or a control ASO for 4 wk, followed by metabolic assessments. SRC1 ASO did not alter basal EGP or expression of gluconeogenic enzymes. Instead, SRC1 ASO increased insulin-stimulated whole body glucose disposal by ~30%, which was attributable largely to an increase in insulin-stimulated muscle glucose uptake. This was associated with an approximately sevenfold increase in adipose expression of lipocalin-type prostaglandin D2 synthase, a previously reported regulator of insulin sensitivity, and an approximately 70% increase in plasma PGD2 concentration. Muscle insulin signaling, AMPK activation, and tissue perfusion were unchanged. Although GLUT4 content was unchanged, SRC1 ASO increased the cleavage of tether-containing UBX domain for GLUT4, a regulator of GLUT4 translocation. These studies point to a novel role of adipose SRC1 as a regulator of insulin-stimulated muscle glucose uptake.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Resistência à Insulina , Músculo Esquelético/efeitos dos fármacos , Coativador 1 de Receptor Nuclear/antagonistas & inibidores , Oligodesoxirribonucleotídeos Antissenso/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/enzimologia , Tecido Adiposo/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Transportador de Glucose Tipo 4/agonistas , Transportador de Glucose Tipo 4/química , Transportador de Glucose Tipo 4/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/agonistas , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/agonistas , Lipocalinas/genética , Lipocalinas/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Coativador 1 de Receptor Nuclear/genética , Coativador 1 de Receptor Nuclear/metabolismo , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Prostaglandina D2/sangue , Prostaglandina D2/metabolismo , Domínios e Motivos de Interação entre Proteínas , Proteólise/efeitos dos fármacos , Ratos Sprague-Dawley
3.
IEEE Trans Med Imaging ; 33(6): 1275-89, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24893257

RESUMO

Quantitative analysis of left ventricular deformation can provide valuable information about the extent of disease as well as the efficacy of treatment. In this work, we develop an adaptive multi-level compactly supported radial basis approach for deformation analysis in 3D+time echocardiography. Our method combines displacement information from shape tracking of myocardial boundaries (derived from B-mode data) with mid-wall displacements from radio-frequency-based ultrasound speckle tracking. We evaluate our methods on open-chest canines (N=8) and show that our combined approach is better correlated to magnetic resonance tagging-derived strains than either individual method. We also are able to identify regions of myocardial infarction (confirmed by postmortem analysis) using radial strain values obtained with our approach.


Assuntos
Ecocardiografia Quadridimensional/métodos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Animais , Cães , Masculino , Movimento , Infarto do Miocárdio , Miocárdio/patologia
4.
Med Image Anal ; 18(2): 253-71, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24292554

RESUMO

This paper presents a dynamical appearance model based on sparse representation and dictionary learning for tracking both endocardial and epicardial contours of the left ventricle in echocardiographic sequences. Instead of learning offline spatiotemporal priors from databases, we exploit the inherent spatiotemporal coherence of individual data to constraint cardiac contour estimation. The contour tracker is initialized with a manual tracing of the first frame. It employs multiscale sparse representation of local image appearance and learns online multiscale appearance dictionaries in a boosting framework as the image sequence is segmented frame-by-frame sequentially. The weights of multiscale appearance dictionaries are optimized automatically. Our region-based level set segmentation integrates a spectrum of complementary multilevel information including intensity, multiscale local appearance, and dynamical shape prediction. The approach is validated on twenty-six 4D canine echocardiographic images acquired from both healthy and post-infarct canines. The segmentation results agree well with expert manual tracings. The ejection fraction estimates also show good agreement with manual results. Advantages of our approach are demonstrated by comparisons with a conventional pure intensity model, a registration-based contour tracker, and a state-of-the-art database-dependent offline dynamical shape model. We also demonstrate the feasibility of clinical application by applying the method to four 4D human data sets.


Assuntos
Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Infarto do Miocárdio/diagnóstico por imagem , Algoritmos , Animais , Artefatos , Cães , Endocárdio/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Magn Reson Med ; 70(3): 766-75, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23044637

RESUMO

A high-temporal resolution 2D flow pathline analysis method to study early diastolic filling is presented. Filling patterns in normal volunteers (n = 8) and canine animals [baseline (n = 1) and infarcted (n = 6)] are studied. Data are acquired using spatial modulation of magnetization with polarity alternating velocity encoding, which permits simultaneous quantification of 1D blood velocities (using phase contrast encoding) and myocardial strain (using spatial modulation of magnetization tagging and harmonic phase analysis) at high-temporal resolution of 14 ms within a single breath hold. Virtual emitter particles, released from the mitral valve plane every time frame during rapid filling, are tracked to depict the 2D pathlines on the imaged plane. The pathline regional distribution is compared with myocardial longitudinal strains and to regional pressure gradients. Quantitative analysis of net kinetic energy of pathlines is finally performed. Our results demonstrate a linear correlation (r(2) = 0.85) between pathline spatial distribution and myocardial strain. Peak net kinetic energy of 0.06 ± 0.01 mJ in normal volunteers, 0.043 mJ in baseline dog, 0.143 ± 0.03 mJ in infarcted dogs with nominal flow dysfunction, and 0.016 ± 0.007 mJ in infarcted dogs with severe flow dysfunction is observed. In conclusion, 2D pathline analysis provides a direct regional assessment of early diastolic filling patterns and is sensitive to abnormalities in early diastolic filling.


Assuntos
Infarto do Miocárdio/fisiopatologia , Função Ventricular Esquerda/fisiologia , Adulto , Animais , Diástole , Cães , Feminino , Voluntários Saudáveis , Ventrículos do Coração , Humanos , Masculino
6.
Artigo em Inglês | MEDLINE | ID: mdl-24505744

RESUMO

Dictionary learning has been shown to be effective in exploiting spatiotemporal coherence for echocardiographic segmentation. To overcome the limitations of previous methods, we present a stochastic online dictionary learning approach for segmenting left ventricular borders from 4D echocardiography. It is based on stochastic approximations and processes a mini-batch of samples at a time, which results in lower memory consumption and lower computational cost than classical batch algorithms. In contrast to the previous methods, where dictionaries and their weights are optimized only on the most recently segmented frame, our stochastic online learning procedure optimizes the dictionaries and the corresponding weights by aggregating all the past information while adapting them to the dynamically changing data. The rate of updating the past information is controlled and varied according to the appearance scale to seek a balance between old and new information. Results on 26 4D echocardiographic images show the proposed method is more accurate, more robust, and faster than the previous batch algorithm.


Assuntos
Algoritmos , Inteligência Artificial , Ecocardiografia Quadridimensional/métodos , Interpretação de Imagem Assistida por Computador/métodos , Infarto do Miocárdio/diagnóstico por imagem , Reconhecimento Automatizado de Padrão/métodos , Técnica de Subtração , Animais , Interpretação Estatística de Dados , Cães , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Processos Estocásticos
7.
Artigo em Inglês | MEDLINE | ID: mdl-23286114

RESUMO

The spatio-temporal coherence in data plays an important role in echocardiographic segmentation. While learning offline dynamical priors from databases has received considerable attention, these priors may not be suitable for post-infarct patients and children with congenital heart disease. This paper presents a dynamical appearance model (DAM) driven by individual inherent data coherence. It employs multi-scale sparse representation of local appearance, learns online multiscale appearance dictionaries as the image sequence is segmented sequentially, and integrates a spectrum of complementary multiscale appearance information including intensity, multiscale local appearance, and dynamical shape predictions. It overcomes the limitations of database-driven statistical models and applies to a broader range of subjects. Results on 26 4D canine echocardiographic images acquired from both healthy and post-infarct subjects show that our method significantly improves segmentation accuracy and robustness compared to a conventional intensity model and our previous single-scale sparse representation method.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca/métodos , Ecocardiografia Tridimensional/métodos , Interpretação de Imagem Assistida por Computador/métodos , Modelos Cardiovasculares , Disfunção Ventricular Esquerda/diagnóstico por imagem , Simulação por Computador , Humanos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
Magn Reson Med ; 66(6): 1627-38, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21630348

RESUMO

A novel MR imaging technique, spatial modulation of magnetization with polarity alternating velocity encoding (SPAMM-PAV), is presented to simultaneously examine the left ventricular early diastolic temporal relationships between myocardial deformation and intra-cavity hemodynamics with a high temporal resolution of 14 ms. This approach is initially evaluated in a dynamic flow and tissue mimicking phantom. A comparison of regional longitudinal strains and intra-cavity pressure differences (integration of computed in-plane pressure gradients within a selected region) in relation to mitral valve inflow velocities is performed in eight normal volunteers. Our results demonstrate that apical regions have higher strain rates (0.145 ± 0.005 %/ms) during the acceleration period of rapid filling compared to mid-ventricular (0.114 ± 0.007 %/ms) and basal regions (0.088 ± 0.009 %/ms), and apical strain curves plateau at peak mitral inflow velocity. This pattern is reversed during the deceleration period, when the strain-rates in the basal regions are the highest (0.027 ± 0.003 %/ms) due to ongoing basal stretching. A positive base-to-apex gradient in peak pressure difference is observed during acceleration, followed by a negative base-to-apex gradient during deceleration. These studies shed insight into the regional volumetric and pressure difference changes in the left ventricle during early diastolic filling.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Ventrículos do Coração/anatomia & histologia , Interpretação de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Algoritmos , Módulo de Elasticidade/fisiologia , Humanos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Circ Cardiovasc Imaging ; 4(4): 381-91, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21505092

RESUMO

BACKGROUND: Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction after MI remain undefined. METHODS AND RESULTS: MI was surgically induced in pigs (n = 23) and cine magnetic resonance (MR) and dual-isotope hybrid single-photon emission CT (SPECT)/CT imaging obtained using thallium-201 and a technetium-99m-labeled MMP targeted tracer ((99m)Tc-RP805) at 1, 2, and 4 weeks post-MI along with controls (n = 5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial (99m)Tc-RP805 retention. MMP activation as assessed by in vivo and ex vivo (99m)Tc-RP805 imaging and retention studies was increased nearly 4-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y = 31.34e(0.48x), P = 0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional (99m)Tc-RP805 uptake and ex vivo MMP-2 activity. CONCLUSIONS: A novel, multimodality, noninvasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased (99m)Tc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of thallium-201 perfusion. The (99m)Tc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling.


Assuntos
Metaloproteinases da Matriz/metabolismo , Infarto do Miocárdio/enzimologia , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Remodelação Ventricular/fisiologia , Animais , Processamento de Imagem Assistida por Computador , Imagem Cinética por Ressonância Magnética , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Suínos , Radioisótopos de Tálio
10.
J Nucl Med ; 52(3): 453-60, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21321271

RESUMO

UNLABELLED: Accurate and reproducible SPECT quantification of myocardial molecular processes remains a challenge because of the complication of heterogeneous background and extracardiac activity adjacent to the heart, which causes errors in the estimation of myocardial focal tracer uptake. Our aim in this study was to introduce a heuristic method for the correction of extracardiac activity into SPECT quantification and validate the modified quantification method for accuracy and reproducibility using a canine model. METHODS: Dual-isotope-targeted (99m)Tc and (201)Tl perfusion SPECT images were acquired using a hybrid SPECT/CT camera in 6 dogs at 2 wk after myocardial infarction. Images were reconstructed with and without CT-based attenuation correction, and the reconstructed SPECT images were filtered and quantified simultaneously with incorporation of extracardiac radioactivity correction, gaussian fitting, and total-count sampling. Absolute myocardial focal tracer uptake was quantified from SPECT images using 3 different normal limits (maximum entropy [ME], mean-squared-error minimization [MSEM], and global minimum [GM]). SPECT-quantified percentage injected dose (%ID) was calculated and compared with the well-counted radioactivity measured from the postmortem myocardial tissue. SPECT quantitative processing was performed by 2 different individuals with extensive experience in cardiac image processing, to assess reproducibility of the quantitative analysis. RESULTS: Correlations between SPECT-quantified and well-counted %IDs using 3 different normal limits were excellent (ME: r = 0.82, y = 0.932 x - 0.0102; MSEM: r = 0.73, y = 1.1413 x - 0.0052; and GM: r = 0.7, y = 1.2147 x - 0.0002). SPECT quantification using ME normal limits resulted in an underestimation of %ID, as compared with well-counted %ID. Myocardial focal tracer uptake quantified from SPECT images without CT-based attenuation correction was significantly lower than that with the attenuation correction. The %IDs quantified from attenuation-corrected SPECT images using MSEM and GM normal limits were not significantly different from well-counted %IDs. Reproducibility of the SPECT quantitative analysis was excellent (ME: r = 0.98, y = 0.9221 x + 0.0001; MSEM: r = 0.97, y = 0.9357 x + 0.0004; and GM: r = 0.96, y = 0.9026 x + 0.001). CONCLUSION: Our SPECT/CT quantification algorithm for the assessment of regional radioactivity may allow for accurate and reproducible serial noninvasive evaluation of molecularly targeted tracers in the myocardium.


Assuntos
Imagem Molecular/métodos , Imagem de Perfusão do Miocárdio/métodos , Miocárdio/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Técnica de Subtração , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Animais , Cães , Feminino , Coração/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Taxa de Depuração Metabólica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual
11.
Med Image Anal ; 15(1): 96-111, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20869902

RESUMO

Small animal X-ray computed tomographic (microCT) imaging of the lower extremities permits evaluation of arterial growth in models of hindlimb ischemia, and when applied serially can provide quantitative information about disease progression and aid in the evaluation of therapeutic interventions. The quantification of changes in tissue perfusion and concentration of molecular markers concurrently obtained using nuclear imaging requires the ability to non-rigidly register the microCT images over time, a task made more challenging by the potentially large changes in the positions of the legs due to articulation. While non-rigid registration methods have been extensively used in the evaluation of individual organs, application in whole body imaging has been limited, primarily because the scale of possible displacements and deformations is large resulting in poor convergence of most methods. In this paper we present a new method based on the extended demons algorithm that uses a level-set representation of the body contour and skeletal structure as an input. The proposed serial registration method reflects the natural physical moving combination of mouse anatomy in which the movement of bones is the framework for body movements, and the movement of skin constrains the detailed movements of the specific segmented body regions. We applied our method to both the registration of serial microCT mouse images and the quantification of microSPECT component of the serially hybrid microCT-SPECT images demonstrating improved performance as compared to existing registration techniques.


Assuntos
Algoritmos , Extremidade Inferior/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Microtomografia por Raio-X/métodos , Animais , Camundongos , Modelos Estatísticos
12.
Med Phys ; 37(5): 2233-46, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20527557

RESUMO

PURPOSE: We present an iterative framework for CT reconstruction from transmission ultrasound data which accurately and efficiently models the strong refraction effects that occur in our target application: Imaging the female breast. METHODS: Our refractive ray tracing framework has its foundation in the fast marching method (FNMM) and it allows an accurate as well as efficient modeling of curved rays. We also describe a novel regularization scheme that yields further significant reconstruction quality improvements. A final contribution is the development of a realistic anthropomorphic digital breast phantom based on the NIH Visible Female data set. RESULTS: Our system is able to resolve very fine details even in the presence of significant noise, and it reconstructs both sound speed and attenuation data. Excellent correspondence with a traditional, but significantly more computationally expensive wave equation solver is achieved. CONCLUSIONS: Apart from the accurate modeling of curved rays, decisive factors have also been our regularization scheme and the high-quality interpolation filter we have used. An added benefit of our framework is that it accelerates well on GPUs where we have shown that clinical 3D reconstruction speeds on the order of minutes are possible.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Tomografia/métodos , Ultrassonografia Mamária/métodos , Algoritmos , Animais , Estudos de Viabilidade , Feminino , Humanos , Imageamento Tridimensional , Imagens de Fantasmas , Fatores de Tempo
13.
JACC Cardiovasc Imaging ; 2(10): 1198-208, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19833310

RESUMO

OBJECTIVES: The purpose of this study was to compare a selective A(2A) adenosine receptor agonist (regadenoson) with adenosine in clinically relevant canine models with regard to effects on hemodynamics and thallium-201 ((201)Tl) and technetium-99m ((99m)Tc)-sestaMIBI biodistribution and kinetics. BACKGROUND: The clinical application of vasodilator stress for perfusion imaging requires consideration of the effects of these vasodilating agents on systemic hemodynamics, coronary flow, and radiotracer uptake and clearance kinetics. METHODS: Sequential imaging and arterial blood sampling was performed on control, anesthetized closed-chest canines (n = 7) to evaluate radiotracer biodistribution and kinetics after either a bolus administration of regadenoson (2.5 microg/kg) or 4.5-min infusion of adenosine (280 microg/kg). The effects of regadenoson on coronary flow and myocardial radiotracer uptake were then evaluated in an open-chest canine model of a critical stenosis (n = 7). Results from ex vivo single-photon emission computed tomography were compared with tissue well-counting. RESULTS: The use of regadenoson compared favorably with adenosine in regard to the duration and magnitude of the hemodynamic effects and the effect on (201)Tl and (99m)Tc-sestaMIBI biodistribution and kinetics. The arterial blood clearance half-time was significantly faster for (99m)Tc-sestaMIBI (regadenoson: 1.4 +/- 0.03 min; adenosine: 1.5 +/- 0.08 min) than for (201)Tl (regadenoson: 2.5 +/- 0.16 min, p < 0.01; adenosine: 2.7 +/- 0.04 min, p < 0.01) for both vasodilator stressors. The relative microsphere flow deficit (0.34 +/- 0.02%) during regadenoson stress was significantly greater than the relative perfusion defect with (99m)Tc-sestaMIBI (0.69 +/- 0.03%, p < 0.001) or (201)Tl (0.53 +/- 0.02%, p < 0.001), although (201)Tl tracked the flow deficit within the ischemic region better than (99m)Tc-sestaMIBI. The perfusion defect score was larger with (201)Tl (22 +/- 2.8% left ventricular) than with (99m)Tc-sestaMIBI (17 +/- 1.7% left ventricular, p < 0.05) on ex vivo single-photon emission computed tomography images. CONCLUSIONS: The bolus administration of regadenoson produced a hyperemic response comparable to a standard infusion of adenosine. The biodistribution and clearance of both (201)Tl and (99m)Tc-sestaMIBI during regadenoson were similar to adenosine vasodilation. Ex vivo perfusion images under the most ideal conditions permitted detection of a critical stenosis, although (201)Tl offered significant advantages over (99m)Tc-sestaMIBI for perfusion imaging during regadenoson vasodilator stress.


Assuntos
Agonistas do Receptor A2 de Adenosina , Adenosina/farmacologia , Circulação Coronária/efeitos dos fármacos , Estenose Coronária/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Purinas/farmacologia , Pirazóis/farmacologia , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio Tc 99m Sestamibi/farmacocinética , Radioisótopos de Tálio/farmacocinética , Tomografia Computadorizada de Emissão de Fóton Único , Vasodilatadores/farmacologia , Doença Aguda , Adenosina/administração & dosagem , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Doença Crônica , Estenose Coronária/metabolismo , Estenose Coronária/fisiopatologia , Modelos Animais de Doenças , Cães , Hiperemia/diagnóstico por imagem , Hiperemia/fisiopatologia , Infusões Intravenosas , Injeções Intravenosas , Taxa de Depuração Metabólica , Miocárdio/metabolismo , Miocárdio/patologia , Valor Preditivo dos Testes , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Compostos Radiofarmacêuticos/sangue , Receptor A2A de Adenosina/metabolismo , Tecnécio Tc 99m Sestamibi/sangue , Radioisótopos de Tálio/sangue , Distribuição Tecidual , Vasodilatadores/administração & dosagem
14.
J Nucl Med ; 50(8): 1356-63, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19617325

RESUMO

UNLABELLED: Previous studies by our group have demonstrated the feasibility of noninvasive imaging of alpha(v) integrin to assess temporal and spatial changes in peripheral and myocardial angiogenesis. In this study, we validate the reproducibility, accuracy, and applicability of a new semiautomated noninvasive approach for serial quantitative evaluation of targeted micro-SPECT/CT images of peripheral angiogenesis in wild-type and endothelial nitric oxide sythase (eNOS)-deficient (eNOS-/-) mice subjected to hindlimb ischemia. METHODS: Mice (n = 15) underwent surgical ligation of the right femoral artery to induce unilateral hindlimb ischemia. One week after ligation, a (99m)Tc-labeled cyclic-Arg-Gly-Asp peptide targeted at alpha(v) integrin (NC100692, n = 10) or a (99m)Tc-labeled negative control (AH-111744, n = 5) was injected, and 60 min later in vivo micro-SPECT/CT images were acquired. Mice were euthanized, tissue from proximal and distal hindlimb was excised for gamma-well counting (GWC) of radiotracer activity, and ischemic-to-nonischemic (I/NI) ratio was calculated. Micro-SPECT/CT images were analyzed using a new semiautomated approach that applies complex volumes of interest (VOIs) derived from segmentation of the micro-CT images onto micro-SPECT images to calculate I/NI activity ratios for the proximal and distal hindlimb. Studies were reprocessed for determination of intra- and interobserver variability. To compare 3-dimensional (3D) VOI analysis with traditional manual 2-dimensional region-of-interest (ROI) analysis of maximum-intensity-projection images, micro-SPECT images were summed onto a single anterior-posterior projection. Rectangular ROIs were manually drawn and I/NI ratio calculated. Our new 3D analysis approach was applied to additional groups of mice (eNOS-/-, n = 5; wild-type, n = 3) imaged before and 1 and 4 wk after femoral artery resection. RESULTS: Our new semiautomated approach for the evaluation of images of alpha(v) integrin targeted with micro-SPECT/CT demonstrated both a high intra- and interobserver variability (R(2) = 0.997) and an accuracy (R(2) = 0.780) for estimation of relative radiotracer activity relative to GWC. Analysis of serial micro-SPECT/CT images demonstrated a significant increase in relative NC100692 retention in the ischemic hindlimb of both wild-type and eNOS-/- mice at 1 wk after surgery. There was a significant (approximately 25%) decrease in radiotracer uptake in eNOS-/- mice relative to wild-type animals, which was not observed at baseline or 4 wk after ligation. CONCLUSION: A new semiautomated analysis of images of alpha(v) integrin targeted with micro-SPECT/CT provides a noninvasive approach for serial quantitative evaluation of peripheral angiogenesis. The reproducibility and accuracy of this approach allows for quantitative analysis of serial targeted molecular images of lower extremities, has applicability to other targeted SPECT or PET radiotracers, and may have implications for clinical imaging in patients with peripheral arterial disease.


Assuntos
Proteínas Angiogênicas/metabolismo , Angiografia/métodos , Interpretação de Imagem Assistida por Computador/métodos , Integrina alfaV/metabolismo , Neovascularização Fisiológica/fisiologia , Peptídeos Cíclicos/farmacocinética , Algoritmos , Animais , Aumento da Imagem/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tecnécio/farmacocinética
15.
Med Image Anal ; 13(1): 49-61, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18678521

RESUMO

Modern medical imaging techniques enable the acquisition of in vivo high resolution images of the vascular system. Most common methods for the detection of vessels in these images, such as multiscale Hessian-based operators and matched filters, rely on the assumption that at each voxel there is a single cylinder. Such an assumption is clearly violated at the multitude of branching points that are easily observed in all, but the most focused vascular image studies. In this paper, we propose a novel method for detecting vessels in medical images that relaxes this single cylinder assumption. We directly exploit local neighborhood intensities and extract characteristics of the local intensity profile (in a spherical polar coordinate system) which we term as the polar neighborhood intensity profile. We present a new method to capture the common properties shared by polar neighborhood intensity profiles for all the types of vascular points belonging to the vascular system. The new method enables us to detect vessels even near complex extreme points, including branching points. Our method demonstrates improved performance over standard methods on both 2D synthetic images and 3D animal and clinical vascular images, particularly close to vessel branching regions.


Assuntos
Algoritmos , Angiografia/métodos , Inteligência Artificial , Vasos Sanguíneos/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Reconhecimento Automatizado de Padrão/métodos , Animais , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ovinos , Tomografia Computadorizada por Raios X/métodos
16.
Med Image Comput Comput Assist Interv ; 12(Pt 1): 688-95, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20426048

RESUMO

We present a new method for the non-rigid registration of serial mouse microCT images which undergo potentially large changes in the positions of the legs due to articulation. While non-rigid registration methods have been extensively used in the evaluation of individual organs, application in whole body imaging has been limited, primarily because the scale of possible displacements and deformations is large resulting in poor convergence of most methods. Our method is based on the extended demons algorithm that uses a level-set representation of the mouse skin and skeleton as an input, and composed of three steps reflecting the natural physical movements of bony structures. We applied our method to the registration of serial microCT mouse images demonstrating encouraging performances as compared to competitive techniques.


Assuntos
Membro Posterior/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/veterinária , Reconhecimento Automatizado de Padrão/métodos , Técnica de Subtração/veterinária , Tomografia Computadorizada por Raios X/veterinária , Imagem Corporal Total/veterinária , Algoritmos , Animais , Aumento da Imagem/métodos , Camundongos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
IEEE Trans Vis Comput Graph ; 14(6): 1603-10, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18989016

RESUMO

The effective visualization of vascular structures is critical for diagnosis, surgical planning as well as treatment evaluation. In recent work, we have developed an algorithm for vessel detection that examines the intensity profile around each voxel in an angiographic image and determines the likelihood that any given voxel belongs to a vessel; we term this the "vesselness coefficient" of the voxel. Our results show that our algorithm works particularly well for visualizing branch points in vessels. Compared to standard Hessian based techniques, which are fine-tuned to identify long cylindrical structures, our technique identifies branches and connections with other vessels. Using our computed vesselness coefficient, we explore a set of techniques for visualizing vasculature. Visualizing vessels is particularly challenging because not only is their position in space important for clinicians but it is also important to be able to resolve their spatial relationship. We applied visualization techniques that provide shape cues as well as depth cues to allow the viewer to differentiate between vessels that are closer from those that are farther. We use our computed vesselness coefficient to effectively visualize vasculature in both clinical neurovascular x-ray computed tomography based angiography images, as well as images from three different animal studies. We conducted a formal user evaluation of our visualization techniques with the help of radiologists, surgeons, and other expert users. Results indicate that experts preferred distance color blending and tone shading for conveying depth over standard visualization techniques.


Assuntos
Algoritmos , Angiografia/métodos , Inteligência Artificial , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Reconhecimento Automatizado de Padrão/métodos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
J Appl Physiol (1985) ; 104(5): 1504-12, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18356482

RESUMO

The alphavbeta3-integrin is expressed in angiogenic vessels in response to hypoxia and represents a potential novel target for imaging myocardial angiogenesis. This study evaluated the feasibility of noninvasively tracking hypoxia-induced alphavbeta3-integrin activation within the myocardium as a marker of angiogenesis early after myocardial infarction. Acute myocardial infarction was produced by coronary artery occlusion in rodent and canine studies. A novel (111)In-labeled radiotracer targeted at the alphavbeta3-integrin ((111)In-RP748) was used to localize regions of hypoxia-induced angiogenesis early after infarction. In rodent studies, the specificity of (111)In-RP748 for alphavbeta3-integrin was confirmed with a negative control compound ((111)In-RP790), and regional uptake of these compounds correlated with (201)Tl perfusion and a (99m)Tc-labeled nitroimidazole (BRU59-21), which was used as a quantitative marker of myocardial hypoxia. The ex vivo analysis demonstrated that only (111)In-RP748 was selectively retained in infarcted regions with reduced (201)Tl perfusion and correlated with uptake of BRU59-21. In canine studies, myocardial uptake of (111)In-RP748 was assessed using in vivo single-photon-emission computed tomography (SPECT), ex vivo planar imaging, and gamma well counting of myocardial tissue and correlated with (99m)Tc-labeled 2-methoxy-2-methyl-propyl-isonitrile ((99m)Tc-sestamibi) perfusion. Dual-radiotracer in vivo SPECT imaging of (111)In-RP748 and (99m)Tc-sestamibi provided visualization of (111)In-RP748 uptake within the infarct region, which was confirmed by ex vivo planar imaging of excised myocardial slices. Myocardial (111)In-RP748 retention was associated with histological evidence of alphavbeta3-integrin expression/activation in the infarct region. (111)In-RP748 imaging provides a novel noninvasive approach for evaluation of hypoxia-induced alphavbeta3-integrin activation in myocardium early after infarction and may prove useful for directing and evaluating angiogenic therapies in patients with ischemic heart disease.


Assuntos
Hipóxia/metabolismo , Integrinas/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Actinas/biossíntese , Actinas/genética , Animais , Biomarcadores , Biotransformação/fisiologia , Cães , Compostos Heterocíclicos com 1 Anel , Imidazóis , Imuno-Histoquímica , Integrina alfaVbeta3/biossíntese , Integrina alfaVbeta3/genética , Masculino , Infarto do Miocárdio/patologia , Isquemia Miocárdica/patologia , Miocárdio/patologia , Neovascularização Fisiológica/fisiologia , Compostos Organometálicos , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Ratos , Ratos Sprague-Dawley , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único
19.
Circulation ; 112(20): 3157-67, 2005 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-16275862

RESUMO

BACKGROUND: Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed. METHODS AND RESULTS: MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a (111)In-labeled MMP-targeted radiotracer ((111)In-RP782) and negative control compound ((111)In-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI. Localization of (111)In-RP782 was demonstrated within the MI by microautoradiography. A 334+/-44% increase (P<0.001 versus Ctrl) in relative retention of (111)In-RP782 was confirmed by gamma well counting of myocardium. Subsequent high-resolution dual-isotope planar and hybrid micro-single-photon emission computed tomography/CT imaging studies with an analogous 99mTc-labeled MMP-targeted radiotracer (99mTc-RP805) and 201Tl demonstrated favorable biodistribution and clearance kinetics of 99mTc-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after MI in regions of decreased 201Tl perfusion. Gamma well counting yielded a similar approximately 300% increase in relative myocardial retention of 99mTc-RP805 in MI regions (Ctrl, 102+/-9%; 1 week, 351+/-77%; 2 weeks, 291+/-45%; 3 weeks, 292+/-41%; P<0.05 versus Ctrl). Myocardial uptake in the MI region was also significantly increased approximately 5-fold when expressed as percentage injected dose per gram tissue. There was also a significant 2-fold increase in myocardial activity in remote regions relative to control mice, suggesting activation of MMPs in regions remote from the MI. CONCLUSIONS: This novel noninvasive targeted MMP radiotracer imaging approach holds significant diagnostic potential for in vivo localization of MMP activation and tracking of MMP-mediated post-MI remodeling.


Assuntos
Metaloproteinases da Matriz/metabolismo , Infarto do Miocárdio/diagnóstico por imagem , Cintilografia/métodos , Remodelação Ventricular , Animais , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Remodelação Ventricular/fisiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-16686048

RESUMO

This paper describes a new piecewise rotational transformation model for capturing the articulation of joints such as the hip and the knee. While a simple piecewise rigid model can be applied, such models suffer from discontinuities at the motion boundary leading to both folding and stretching. Our model avoids both of these problems by constructing a provably continuous transformation along the motion interface. We embed this transformation model within the robust point matching framework and demonstrate its successful application to both synthetic data, and to serial x-ray CT mouse images. In the later case, our model captures the articulation of six joints, namely the left/right hip, the left/right knee and the left/right ankle. In the future such a model could be used to initialize non-rigid registrations of images from different subjects, as well as, be embedded in intensity-based and integrated registration algorithms. It could also be applied to human data in cases where articulated motion is an issue (e.g. image guided prostate radiotherapy, lower extremity CT angiography).


Assuntos
Algoritmos , Artrografia/métodos , Imageamento Tridimensional/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Técnica de Subtração , Animais , Inteligência Artificial , Membro Posterior/diagnóstico por imagem , Humanos , Camundongos , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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