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1.
Magn Reson Med ; 89(2): 710-720, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36128887

RESUMEN

PURPOSE: In current intraoperative MRI (IMRI) methods, an iterative approach is used to aim trajectory guides at intracerebral targets: image MR-visible features, determine current aim by fitting model to image, manipulate device, repeat. Infrequent updates are produced by such methods, compared to rapid optically tracked stereotaxy used in the operating room. Our goal was to develop a real-time interactive IMRI method for aiming. METHODS: The current trajectory was computed from two points along the guide's central axis, rather than by imaging the entire device. These points were determined by correlating one-dimensional spokes from a radial sequence with the known cross-sectional projection of the guide. The real-time platform RTHawk was utilized to control MR sequences and data acquisition. On-screen updates were viewed by the operator while simultaneously manipulating the guide to align it with the planned trajectory. Accuracy was quantitated in a phantom, and in vivo validation was demonstrated in nonhuman primates undergoing preclinical gene ( n = 5 $$ n=5 $$ ) and cell ( n = 4 $$ n=4 $$ ) delivery surgeries. RESULTS: Updates were produced at 5 Hz In 10 phantom experiments at a depth of 48 mm, the cannula tip was placed with radial error of (min, mean, max) = (0.16, 0.29, 0.68) mm. Successful in vivo delivery of payloads to all 14 targets was demonstrated across nine surgeries with depths of (min, mean, max) = (33.3, 37.9, 42.5) mm. CONCLUSION: A real-time interactive update rate was achieved, reducing operator fatigue without compromising accuracy. Qualitative interpretation of images during aiming was rendered unnecessary by objectively computing device alignment.


Asunto(s)
Neurocirugia , Animales , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Imagenología Tridimensional
2.
Magn Reson Med ; 71(3): 934-41, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23519837

RESUMEN

PURPOSE: Detection, characterization, and monitoring the treatment of hepatocellular carcinomas (HCC) in patients with cirrhosis is challenging because of their variable and rapid arterial enhancement. Multiphase dynamic contrast-enhanced MRI is used clinically for HCC assessment; however, the method suffers from limited temporal resolution and difficulty in coordinating imaging and breath-hold timing within a narrow temporal window of interest. In this article, a volumetric, high-spatial resolution, and high-temporal resolution dynamic contrast-enhanced liver imaging method for improved detection and characterization of HCC is demonstrated. METHODS: A time-resolved three-dimensional radial acquisition with iterative sensitivity-encoding reconstruction images the entire abdomen and thorax with high spatial and temporal resolution, using real-time three-dimensional fluoroscopy to match the breath hold to contrast arrival. The sequence was tested on 17 subjects, including eight patients with HCC or other hypervascular focal lesions. RESULTS: This technique was successful in acquiring volumetric imaging of the entire liver with 2.1-mm isotropic spatial and true 4-s temporal resolution. CONCLUSION: This technique may be suitable for detecting, characterizing, and monitoring the treatment of HCC. It also holds significant potential for perfusion modeling, which may provide a noninvasive means to rapidly determine the efficacy of chemotherapeutic agents in these tumors over the entire liver volume.


Asunto(s)
Carcinoma Hepatocelular/patología , Aumento de la Imagen/métodos , Imagenología Tridimensional/métodos , Neoplasias Hepáticas/patología , Angiografía por Resonancia Magnética/métodos , Neovascularización Patológica/patología , Algoritmos , Contencion de la Respiración , Simulación por Computador , Medios de Contraste , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Modelos Biológicos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Análisis Espacio-Temporal
3.
Magn Reson Med ; 71(1): 95-104, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23504943

RESUMEN

Radial trajectories facilitate high-resolution balanced steady state free precession (bSSFP) because the efficient gradients provide more time to extend the trajectory in k-space. A number of radial bSSFP methods that support fat-water separation have been developed; however, most of these methods require an environment with limited B0 inhomogeneity. In this work, high-resolution bSSFP with fat-water separation is achieved in more challenging B0 environments by combining a 3D radial trajectory with the IDEAL chemical species separation method. A method to maintain very high resolution within the timing constraints of bSSFP and IDEAL is described using a dual-pass pulse sequence. The sampling of a unique set of radial lines at each echo time is investigated as a means to circumvent the longer scan time that IDEAL incurs as a multiecho acquisition. The manifestation of undersampling artifacts in this trajectory and their effect on chemical species separation are investigated in comparison to the case in which each echo samples the same set of radial lines. This new bSSFP method achieves 0.63 mm isotropic resolution in a 5-min scan and is demonstrated in difficult in vivo imaging environments, including the breast and a knee with ACL reconstruction hardware at 1.5 T.


Asunto(s)
Algoritmos , Lesiones del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/patología , Mama/anatomía & histología , Aumento de la Imagen/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Ligamento Cruzado Anterior/cirugía , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
4.
J Magn Reson Imaging ; 39(4): 853-65, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24395144

RESUMEN

PURPOSE: To develop and demonstrate the feasibility of a new formulation for quantitative perfusion modeling in the liver using interrupted DCE-MRI data acquired during multiple sequential breathholds. MATERIALS AND METHODS: A new mathematical formulation to estimate quantitative perfusion parameters using interrupted data was developed. Using this method, we investigated whether a second degree-of-freedom in the tissue residue function (TRF) improves quality-of-fit criteria when applied to a dual-input single-compartment perfusion model. We subsequently estimated hepatic perfusion parameters using DCE-MRI data from 12 healthy volunteers and 9 cirrhotic patients with a history of hepatocellular carcinoma (HCC); and examined the utility of these estimates in differentiating between healthy liver, cirrhotic liver, and HCC. RESULTS: Quality-of-fit criteria in all groups were improved using a Weibull TRF (2 degrees-of-freedom) versus an exponential TRF (1 degree-of-freedom), indicating nearer concordance of source DCE-MRI data with the Weibull model. Using the Weibull TRF, arterial fraction was greater in cirrhotic versus normal liver (39 ± 23% versus 15 ± 14%, P = 0.07). Mean transit time (20.6 ± 4.1 s versus 9.8 ± 3.5 s, P = 0.01) and arterial fraction (39 ± 23% versus 73 ± 14%, P = 0.04) were both significantly different between cirrhotic liver and HCC, while differences in total perfusion approached significance. CONCLUSION: This work demonstrates the feasibility of estimating hepatic perfusion parameters using interrupted data acquired during sequential breathholds.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/fisiopatología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/fisiopatología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/fisiopatología , Angiografía por Resonancia Magnética/métodos , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Contencion de la Respiración , Simulación por Computador , Diagnóstico Diferencial , Estudios de Factibilidad , Femenino , Humanos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Circulación Hepática , Masculino , Persona de Mediana Edad , Modelos Biológicos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
5.
Magn Reson Med ; 69(2): 509-15, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22488532

RESUMEN

Non-Cartesian imaging sequences and navigational methods can be more sensitive to scanner imperfections that have little impact on conventional clinical sequences, an issue which has repeatedly complicated the commercialization of these techniques by frustrating transitions to multicenter evaluations. One such imperfection is phase errors caused by resonant frequency shifts from eddy currents induced in the cryostat by time-varying gradients, a phenomenon known as B(0) eddy currents. These phase errors can have a substantial impact on sequences that use ramp sampling, bipolar gradients, and readouts at varying azimuthal angles. We present a method for measuring and correcting phase errors from B(0) eddy currents and examine the results on two different scanner models. This technique yields significant improvements in image quality for high-resolution joint imaging on certain scanners. This result suggests that correcting short-time B(0) eddy currents that do not affect conventional clinical sequences may simplify the adoption of non-Cartesian methods.


Asunto(s)
Algoritmos , Artefactos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
6.
Stereotact Funct Neurosurg ; 91(3): 153-61, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23445991

RESUMEN

BACKGROUND: Delivery of multiple collinear payloads utilizing convection-enhanced delivery (CED) has historically been performed by retraction of a needle or catheter from the most distal delivery site. Few studies have addressed end-infusion morphology and associated payload reflux in stacked and collinear infusions, and studies comparing the advancement with the retraction mode are lacking. OBJECTIVE: To compare advancement versus retraction mode infusion results. METHODS: Infusion cloud pairs were created with the advancement and retraction technique in agarose gel using both open end-port SmartFlow (SF) and valve tip (VT) catheter infusion systems. Backflow, radius of infusion, and morphology were assessed. RESULTS: Infusions with the SF catheter, in contrast to the VT catheter, exhibited significantly more backflow in retraction mode at the shallow infusion site. Infusion morphology differed with the second infusion after retraction: the infusate at the proximal site first filling the channel left by the retraction and then being convected into gel in a pronouncedly non-spherical shape during the second infusion. CONCLUSIONS: Significant differences in cloud morphology were noted with respect to external catheter geometry with retraction versus penetration between infusions in an agarose gel model of the brain. Further study is warranted to determine optimal protocols for human clinical trials employing CED with multiple collinear payloads.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Enfermedad de Parkinson/tratamiento farmacológico , Encéfalo , Catéteres , Convección , Geles , Humanos
7.
Magn Reson Med ; 63(2): 282-9, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20099322

RESUMEN

Fat/water separation methods such as fluctuating equilibrium magnetic resonance and linear combination steady-state free precession have not yet been successfully implemented at 3.0 T due to extreme limitations on the time available for spatial encoding with the increase in magnetic field strength. We present a method to utilize a three-dimensional radial sequence combined with linear combination steady-state free precession at 3.0 T to take advantage of the increased signal levels over 1.5 T and demonstrate high spatial resolution compared to Cartesian techniques. We exploit information from the two half-echoes within each pulse repetition time to correct the accumulated phase on a point-by-point basis, thereby fully aligning the phase of both half-echoes. The correction provides reduced sensitivity to static field (B(0)) inhomogeneity and robust fat/water separation. Resultant images in the knee joint demonstrate the necessity of such a correction, as well as the increased isotropic spatial resolution attainable at 3.0 T. Results of a clinical study comparing this sequence to conventional joint imaging sequences are included.


Asunto(s)
Algoritmos , Artefactos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
8.
J Magn Reson Imaging ; 32(4): 943-52, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20882625

RESUMEN

PURPOSE: To provide a framework for characterizing the frequency response of multipoint chemical shift based species separation techniques. MATERIALS AND METHODS: Multipoint chemical shift based species separation techniques acquire complex images at multiple echo times and perform maximum likelihood estimation to decompose signal from different species into separate images. In general, after a nonlinear process of estimating and demodulating the field map, these decomposition methods are linear transforms from the echo-time domain to the chemical-shift-frequency domain, analogous to the discrete Fourier transform (DFT). In this work we describe a technique for finding the magnitude and phase of chemical shift decomposition for input signals over a range of frequencies using numerical and experimental modeling and examine several important cases of species separation. RESULTS: Simple expressions can be derived to describe the response to a wide variety of input signals. Agreement between numerical modeling and experimental results is very good. CONCLUSION: Chemical shift-based species separation is linear, and therefore can be fully described by the magnitude and phase curves of the frequency response. The periodic nature of the frequency response has important implications for the robustness of various techniques for resolving ambiguities in field inhomogeneity.


Asunto(s)
Tejido Adiposo/química , Agua Corporal/química , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Algoritmos , Análisis de Fourier , Humanos , Modelos Químicos , Modelos Estadísticos , Modelos Teóricos , Fantasmas de Imagen , Siliconas/química
9.
Magn Reson Med ; 62(6): 1466-76, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19877274

RESUMEN

Non-Cartesian and rapid imaging sequences are more sensitive to scanner imperfections such as gradient delays and eddy currents. These imperfections vary between scanners and over time and can be a significant impediment to successful implementation and eventual adoption of non-Cartesian techniques by scanner manufacturers. Differences between the k-space trajectory desired and the trajectory actually acquired lead to misregistration and reduction in image quality. While early calibration methods required considerable scan time, more recent methods can work more quickly by making certain approximations. We examine a rapid gradient calibration procedure applied to multiecho three-dimensional projection reconstruction (3DPR) acquisitions in which the calibration runs as part of every scan. After measuring the trajectories traversed for excitations on each of the orthogonal gradient axes, trajectories for the oblique projections actually acquired during the scan are synthesized as linear combinations of these measurements. The ability to do rapid calibration depends on the assumption that gradient errors are linear and time-invariant (LTI). This work examines the validity of these assumptions and shows that the assumption of linearity is reasonable, but that gradient errors can vary over short time periods (due to changes in gradient coil temperature) and thus it is important to use calibration data matched to the scan data.


Asunto(s)
Algoritmos , Artefactos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Simulación por Computador , Modelos Biológicos , Modelos Estadísticos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Factores de Tiempo
10.
Magn Reson Med ; 62(6): 1543-56, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19785015

RESUMEN

The purpose of this work is to detect dynamic gas trapping in three dimensions during forced exhalation at isotropic high spatial resolution and high temporal resolution using hyperpolarized helium-3 MRI. Ten subjects underwent hyperpolarized helium-3 MRI and multidetector CT. MRI was performed throughout inspiration, breath-hold, and forced expiration. A multiecho three-dimensional projection acquisition was used to improve data collection efficiency and an iterative constrained reconstruction was implemented to improve signal to noise ratio (SNR) and increase robustness to motion. Two radiologists evaluated the dynamic MRI and breath-held multidetector CT data for gas and air trapping, respectively. Phantom studies showed the proposed technique significantly improved depiction of moving objects compared to view-sharing methods. Gas trapping was detected using MRI in five of the six asthmatic subjects who displayed air trapping with multidetector CT. Locations in disagreement were found to represent small to moderate regions of air trapping. The proposed technique provides whole-lung three-dimensional imaging of respiration dynamics at high spatial and temporal resolution and compares well to the current standard, multidetector CT. While multidetector CT can provide information about static regional air trapping, it is unable to depict dynamics in a setting more comparable to a spirometry maneuver and explore the longitudinal time evolution of the trapped regions.


Asunto(s)
Asma/diagnóstico , Asma/fisiopatología , Imagen Eco-Planar/métodos , Helio , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Intercambio Gaseoso Pulmonar , Adulto , Algoritmos , Medios de Contraste , Femenino , Humanos , Aumento de la Imagen/métodos , Isótopos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
11.
Biol Psychiatry ; 86(12): 881-889, 2019 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-31422797

RESUMEN

BACKGROUND: An early-life anxious temperament (AT) is a risk factor for the development of anxiety, depression, and comorbid substance abuse. We validated a nonhuman primate model of early-life AT and identified the dorsal amygdala as a core component of AT's neural circuit. Here, we combine RNA sequencing, viral-vector gene manipulation, functional brain imaging, and behavioral phenotyping to uncover AT's molecular substrates. METHODS: In response to potential threat, AT and brain metabolism were assessed in 46 young rhesus monkeys. We identified AT-related transcripts using RNA-sequencing data from dorsal amygdala tissue (including central nucleus of the amygdala [Ce] and dorsal regions of the basal nucleus). Based on the results, we overexpressed the neurotrophin-3 gene, NTF3, in the dorsal amygdala using intraoperative magnetic resonance imaging-guided surgery (n = 5 per group). RESULTS: This discovery-based approach identified AT-related alterations in the expression of well-established and novel genes, including an inverse association between NTRK3 expression and AT. NTRK3 is an interesting target because it is a relatively unexplored neurotrophic factor that modulates intracellular neuroplasticity pathways. Overexpression of the transcript for NTRK3's endogenous ligand, NTF3, in the dorsal amygdala resulted in reduced AT and altered function in AT's neural circuit. CONCLUSIONS: Together, these data implicate neurotrophin-3/NTRK3 signaling in the dorsal amygdala in mediating primate anxiety. More generally, this approach provides an important step toward understanding the molecular underpinnings of early-life AT and will be useful in guiding the development of treatments to prevent the development of stress-related psychopathology.


Asunto(s)
Amígdala del Cerebelo/metabolismo , Ansiedad/metabolismo , Neurotrofina 3/metabolismo , Receptor trkC/metabolismo , Animales , Ansiedad/genética , Modelos Animales de Enfermedad , Expresión Génica , Macaca mulatta , Masculino , Neurotrofina 3/genética
12.
Magn Reson Med ; 60(5): 1122-34, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18956464

RESUMEN

Multiecho chemical shift-based water-fat separation methods are seeing increasing clinical use due to their ability to estimate and correct for field inhomogeneities. Previous chemical shift-based water-fat separation methods used a relatively simple signal model that assumes both water and fat have a single resonant frequency. However, it is well known that fat has several spectral peaks. This inaccuracy in the signal model results in two undesired effects. First, water and fat are incompletely separated. Second, methods designed to estimate T(2) (*) in the presence of fat incorrectly estimate the T(2) (*) decay in tissues containing fat. In this work, a more accurate multifrequency model of fat is included in the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) water-fat separation and simultaneous T(2) (*) estimation techniques. The fat spectrum can be assumed to be constant in all subjects and measured a priori using MR spectroscopy. Alternatively, the fat spectrum can be estimated directly from the data using novel spectrum self-calibration algorithms. The improvement in water-fat separation and T(2) (*) estimation is demonstrated in a variety of in vivo applications, including knee, ankle, spine, breast, and abdominal scans.


Asunto(s)
Tejido Adiposo/anatomía & histología , Tejido Adiposo/química , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Modelos Biológicos , Agua/química , Algoritmos , Animales , Simulación por Computador , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Modelos Químicos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
13.
Cell Transplant ; 26(4): 613-624, 2017 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-27633706

RESUMEN

Induced pluripotent stem cell (iPSC)-derived neurons represent an opportunity for cell replacement strategies for neurodegenerative disorders such as Parkinson's disease (PD). Improvement in cell graft targeting, distribution, and density can be key for disease modification. We have previously developed a trajectory guide system for real-time intraoperative magnetic resonance imaging (RT-IMRI) delivery of infusates, such as viral vector suspensions for gene therapy strategies. Intracerebral delivery of iPSC-derived neurons presents different challenges than viral vectors, including limited cell survival if cells are kept at room temperature for prolonged periods of time, precipitation and aggregation of cells in the cannula, and obstruction during injection, which must be solved for successful application of this delivery approach. To develop procedures suitable for RT-IMRI cell delivery, we first performed in vitro studies to tailor the delivery hardware (e.g., cannula) and defined a range of parameters to be applied (e.g., maximal time span allowable between cell loading in the system and intracerebral injection) to ensure cell survival. Then we performed an in vivo study to evaluate the feasibility of applying the system to nonhuman primates. Our results demonstrate that the RT-IMRI delivery system provides valuable guidance, monitoring, and visualization during intracerebral cell delivery that are compatible with cell survival.


Asunto(s)
Sistemas de Computación , Células Madre Pluripotentes Inducidas/trasplante , Cuidados Intraoperatorios , Imagen por Resonancia Magnética , Neuronas/citología , Animales , Antígenos CD/metabolismo , Encéfalo/patología , Diferenciación Celular , Supervivencia Celular , Geles , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunidad , Inyecciones Intraventriculares , Macaca mulatta , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados
14.
IEEE Trans Med Imaging ; 25(2): 148-57, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16468449

RESUMEN

Time-resolved contrast-enhanced magnetic resonance (MR) angiography (CE-MRA) has gained in popularity relative to X-ray Digital Subtraction Angiography because it provides three-dimensional (3-D) spatial resolution and it is less invasive. We have previously presented methods that improve temporal resolution in CE-MRA while providing high spatial resolution by employing an undersampled 3-D projection (3D PR) trajectory. The increased coverage and isotropic resolution of the 3D PR acquisition simplify visualization of the vasculature from any perspective. We present a new algorithm to develop a set of time-resolved 3-D image volumes by preferentially weighting the 3D PR data according to its acquisition time. An iterative algorithm computes a series of density compensation functions for a regridding reconstruction, one for each time frame, that exploit the variable sampling density in 3D PR. The iterative weighting procedure simplifies the calculation of appropriate density compensation for arbitrary sampling patterns, which improve sampling efficiency and, thus, signal-to-noise ratio and contrast-to-noise ratio, since it is does not require a closed-form calculation based on geometry. Current medical workstations can display these large four-dimensional studies, however, interactive cine animation of the data is only possible at significantly degraded resolution. Therefore, we also present a method for interactive visualization using powerful graphics cards and distributed processing. Results from volunteer and patient studies demonstrate the advantages of dynamic imaging with high spatial resolution.


Asunto(s)
Algoritmos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Angiografía por Resonancia Magnética/métodos , Interfaz Usuario-Computador , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador , Técnica de Sustracción , Factores de Tiempo
15.
Biol Psychiatry ; 80(5): 345-55, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27016385

RESUMEN

BACKGROUND: Nonhuman primate models are critical for understanding mechanisms underlying human psychopathology. We established a nonhuman primate model of anxious temperament (AT) for studying the early-life risk to develop anxiety and depression. Studies have identified the central nucleus of the amygdala (Ce) as an essential component of AT's neural substrates. Corticotropin-releasing factor (CRF) is expressed in the Ce, has a role in stress, and is linked to psychopathology. Here, in young rhesus monkeys, we combined viral vector technology with assessments of anxiety and multimodal neuroimaging to understand the consequences of chronically increased CRF in the Ce region. METHODS: Using real-time intraoperative magnetic resonance imaging-guided convection-enhanced delivery, five monkeys received bilateral dorsal amygdala Ce-region infusions of adeno-associated virus serotype 2 containing the CRF construct. Their cagemates served as unoperated control subjects. AT, regional brain metabolism, resting functional magnetic resonance imaging, and diffusion tensor imaging were assessed before and 2 months after viral infusions. RESULTS: Dorsal amygdala CRF overexpression significantly increased AT and metabolism within the dorsal amygdala. Additionally, we observed changes in metabolism in other AT-related regions, as well as in measures of functional and structural connectivity. CONCLUSIONS: This study provides a translational roadmap that is important for understanding human psychopathology by combining molecular manipulations used in rodents with behavioral phenotyping and multimodal neuroimaging measures used in humans. The results indicate that chronic CRF overexpression in primates not only increases AT but also affects metabolism and connectivity within components of AT's neural circuitry.


Asunto(s)
Ansiedad/patología , Núcleo Amigdalino Central/diagnóstico por imagen , Núcleo Amigdalino Central/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Vías Nerviosas/diagnóstico por imagen , Temperamento , Animales , Anisotropía , Mapeo Encefálico , Hormona Liberadora de Corticotropina/genética , Dependovirus/genética , Imagen de Difusión Tensora , Modelos Animales de Enfermedad , Femenino , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Procesamiento de Imagen Asistido por Computador , Macaca fascicularis , Macaca mulatta , Masculino , Oxígeno/sangre , ARN Mensajero/metabolismo , Transducción Genética
16.
Ann Neurosci ; 20(3): 108-14, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25206026

RESUMEN

BACKGROUND: Convection enhanced delivery (CED) is emerging as a promising infusion toolto facilitate delivery of therapeutic agents into the brain via mechanically controlled pumps. Infusion protocols and catheter design have an important impact on delivery. CED is a valid alternative for systemic administration of agents in clinical trials for cell and gene therapies. Where gel and ex vivo models are not sufficient in modeling the disease, in vivo models allow researchers to better understand the underlying mechanisms of neuron degeneration, which is helpful in finding novel approaches to control the process or reverse the progression. Determining the risks, benefits, and efficacy of new gene therapies introduced via CED will pave a way to enter human clinical trial. PURPOSE: The objective of this study is to compare volume distribution (Vd)/ volume infused (Vi) ratios and backflow measurements following CED infusions in ex vivo versus in vivo non-human primate brain tissue, based on infusion protocols developed in vitro. METHODS: In ex vivo infusions, the first brain received 2 infusions using a balloon catheter at rates of 1 µL/min and 2 µL/min for 30 minutes. The second and third brains received infusions using a valve-tip (VT) catheter at 1 µL/min for 30 minutes. The fourth brain received a total of 45 µL infused at a rate of 1 µL/min for 15 minutes followed by 2 µL/min for 15 minutes. Imaging was performed (SPGR FA34) every 3 minutes. In the in vivo group, 4 subjects received a total of 8 infusions of 50 µL. Subjects 1 and 2 received infusions at 1.0 µL/min using a VT catheter in the left hemisphere and a smart-flow (SF) catheter in the right hemisphere. Subjects 3 and 4 each received 1 infusion in the left and right hemisphere at 1.0 µL/min. RESULTS: MRI calculations of Vd/Vi did not significantly differ from those obtained on post-mortem pathology. The mean measured Vd/Vi of in vivo (5.23 + /-1.67) compared to ex vivo (2.17 + /-1.39) demonstrated a significantly larger Vd/Vi for in vivo by 2.4 times (p = 0.0017). CONCLUSION: We detected higher ratios in the in vivo subjects than in ex vivo. This difference could be explained by the extra cellular space volume fraction. Studies evaluating backflow and morphology use in vivo tissue as a medium are recommended. Further investigation is warranted to evaluate the role blood pressure and heart rate may play in human CED clinical trials.

17.
J Neural Eng ; 9(2): 026009, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22331865

RESUMEN

Convection-enhanced delivery (CED) is an advanced infusion technique used to deliver therapeutic agents into the brain. CED has shown promise in recent clinical trials. Independent verification of published parameters is warranted with benchmark testing of published parameters in applicable models such as gel phantoms, ex vivo tissue and in vivo non-human animal models to effectively inform planned and future clinical therapies. In the current study, specific performance characteristics of two CED infusion catheter systems, such as backflow, infusion cloud morphology, volume of distribution (mm(3)) versus the infused volume (mm(3)) (Vd/Vi) ratios, rate of infusion (µl min(-1)) and pressure (mmHg), were examined to ensure published performance standards for the ERG valve-tip (VT) catheter. We tested the hypothesis that the ERG VT catheter with an infusion protocol of a steady 1 µl min(-1) functionality is comparable to the newly FDA approved MRI Interventions Smart Flow (SF) catheter with the UCSF infusion protocol in an agarose gel model. In the gel phantom models, no significant difference was found in performance parameters between the VT and SF catheter. We report, for the first time, such benchmark characteristics in CED between these two otherwise similar single-end port VT with stylet and end-port non-stylet infusion systems. Results of the current study in agarose gel models suggest that the performance of the VT catheter is comparable to the SF catheter and warrants further investigation as a tool in the armamentarium of CED techniques for eventual clinical use and application.


Asunto(s)
Encéfalo/fisiología , Catéteres , Sistemas de Liberación de Medicamentos , Terapia Genética/métodos , Imagen por Resonancia Magnética/métodos , Modelos Neurológicos , Enfermedad de Parkinson/terapia , Algoritmos , Benchmarking , Materiales Biocompatibles , Colorantes , Computadores , Interpretación Estadística de Datos , Geles , Humanos , Bombas de Infusión Implantables , Enfermedad de Parkinson/genética , Sefarosa
18.
J Magn Reson Imaging ; 30(1): 135-44, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19557728

RESUMEN

PURPOSE: To assess a 3D radial balanced steady-state free precession (SSFP) technique that provides submillimeter isotropic resolution and inherently registered fat and water image volumes in comparison to conventional T2-weighted RARE imaging for lesion characterization in breast magnetic resonance imaging (MRI). MATERIALS AND METHODS: 3D projection SSFP (3DPR-SSFP) combines a dual half-echo radial k-space trajectory with a linear combination fat/water separation technique (linear combination SSFP). A pilot study was performed in 20 patients to assess fat suppression and depiction of lesion morphology using 3DPR-SSFP. For all patients fat suppression was measured for the 3DPR-SSFP image volumes and depiction of lesion morphology was compared against corresponding T2-weighted fast spin echo (FSE) datasets for 15 lesions in 11 patients. RESULTS: The isotropic 0.63 mm resolution of the 3DPR-SSFP sequence demonstrated improved depiction of lesion morphology in comparison to FSE. The 3DPR-SSFP fat and water datasets were available in a 5-minute scan time while average fat suppression with 3DPR-SSFP was 71% across all 20 patients. CONCLUSION: 3DPR-SSFP has the potential to improve the lesion characterization information available in breast MRI, particularly in comparison to conventional FSE. A larger study is warranted to quantify the effect of 3DPR-SSFP on specificity.


Asunto(s)
Adenocarcinoma/patología , Neoplasias de la Mama/patología , Fibroadenoma/patología , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Tejido Adiposo , Agua Corporal , Mama/patología , Quiste Mamario/patología , Femenino , Humanos , Proyectos Piloto
19.
Magn Reson Med ; 59(5): 1151-64, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18429018

RESUMEN

Chemical-shift artifacts associated with non-Cartesian imaging are more complex to model and less clinically acceptable than the bulk fat shift that occurs with conventional spin-warp Cartesian imaging. A novel k-space based iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) approach is introduced that decomposes multiple species while simultaneously correcting distortion of off-resonant species. The new signal model accounts for the additional phase accumulated by off-resonant spins at each point in the k-space acquisition trajectory. This phase can then be corrected by adjusting the decomposition matrix for each k-space point during the final IDEAL processing step with little increase in reconstruction time. The technique is demonstrated with water-fat decomposition using projection reconstruction (PR)/radial, spiral, and Cartesian spin-warp imaging of phantoms and human subjects, in each case achieving substantial correction of chemical-shift artifacts. Simulations of the point-spread-function (PSF) for off-resonant spins are examined to show the nature of the chemical-shift distortion for each acquisition. Also introduced is an approach to improve the signal model for species which have multiple resonant peaks. Many chemical species, including fat, have multiple resonant peaks, although such species are often approximated as a single peak. The improved multipeak decomposition is demonstrated with water-fat imaging, showing a substantial improvement in water-fat separation.


Asunto(s)
Aumento de la Imagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Articulación de la Rodilla/anatomía & histología , Imagen por Resonancia Magnética/métodos , Tejido Adiposo , Algoritmos , Artefactos , Agua Corporal
20.
Magn Reson Med ; 59(5): 1062-71, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18429034

RESUMEN

A method is presented for high-resolution 3D imaging of the whole lung using inhaled hyperpolarized (HP) He-3 MR with multiple half-echo radial trajectories that can accelerate imaging through undersampling. A multiple half-echo radial trajectory can be used to reduce the level of artifact for undersampled 3D projection reconstruction (PR) imaging by increasing the amount of data acquired per unit time for HP He-3 lung imaging. The point spread functions (PSFs) for breath-held He-3 MRI using multiple half-echo trajectories were evaluated using simulations to predict the effects of T(2)* and gas diffusion on image quality. Results from PSF simulations were consistent with imaging results in volunteer studies showing improved image quality with increasing number of echoes using up to 8 half-echoes. The 8-half-echo acquisition is shown to accommodate lost breath-holds as short as 6 sec using a retrospective reconstruction at reduced resolution and also to allow reduced breath-hold time compared with an equivalent Cartesian trajectory. Furthermore, preliminary results from a 3D dynamic inhalation-exhalation maneuver are demonstrated using the 8-half-echo trajectory. Results demonstrate the first high-resolution 3D PR imaging of ventilation and respiratory dynamics in humans using HP He-3 MR.


Asunto(s)
Helio , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional , Imagen por Resonancia Magnética/métodos , Ventilación Pulmonar , Simulación por Computador , Humanos , Fantasmas de Imagen
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