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1.
Magn Reson Imaging ; 103: 162-168, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37541456

RESUMEN

INTRODUCTION: Minimally-invasive surgical techniques for intracerebral hemorrhage (ICH) evacuation use imaging to guide the suction, lysing and/or drainage from the hemorrhage site via various designs. A previous international surgical study has shown that reduction of hematoma volume below 15 ml is indicative of improved long term patient outcomes. The study noted a need for tools to periodically visualize remaining clot during intervention to increase the likelihood of evacuating sufficient clot volumes without endangering rebleeds. Robust segmentation of MRI could guide surgeons and radiologists regarding remaining regions and approaches for prudent evacuation. We thus propose a Convolutional Neural Network (CNN) to identify and autonomously segment clot and peripheral edema in MR images of the brain and generate an estimate of the remaining clot volume. MATERIALS AND METHODS: We used a retrospective, locally-acquired dataset of ICH patient scans taken on 3 T MRI scanners. Three sets of ground truth manual segmentations were independently generated by two imaging scientists and one radiology fellow. Evaluation of clot age was determined based on relative contrast of hemorrhage components and reviewed by a neurosurgeon. Model accuracy was determined by pixel-wise Dice coefficient (DC) calculations between each ground truth manual segmentation and the machine-derived autonomous segmentations. RESULTS: The model produced autonomous segmentations of clot core with an average DC of 0.75 ± 0.21 relative to manual segmentations of the same scans. For edema, it produced segmentations with an average DC of 0.68 ± 0.16 relative to manual. From these pixel-wise segmentations, clot volume can be calculated. Model-produced segmentations underestimated clot volumes by an average of 17% relative to ground-truth. CONCLUSION: The machine learning models were able to identify and segment volumes of ICH components swiftly and accurately.


Asunto(s)
Hemorragia Cerebral , Redes Neurales de la Computación , Humanos , Estudios Retrospectivos , Hemorragia Cerebral/diagnóstico por imagen , Encéfalo , Edema , Imagen por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos
2.
Methods Mol Biol ; 2614: 187-235, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36587127

RESUMEN

With recent advances in cancer therapeutics, there is a great need for improved imaging methods for characterizing cancer onset and progression in a quantitative and actionable way. Collagen, the most abundant extracellular matrix protein in the tumor microenvironment (and the body in general), plays a multifaceted role, both hindering and promoting cancer invasion and progression. Collagen deposition can defend the tumor with immunosuppressive effects, while aligned collagen fiber structures can enable tumor cell migration, aiding invasion and metastasis. Given the complex role of collagen fiber organization and topology, imaging has been a tool of choice to characterize these changes on multiple spatial scales, from the organ and tumor scale to cellular and subcellular level. Macroscale density already aids in the detection and diagnosis of solid cancers, but progress is being made to integrate finer microscale features into the process. Here we review imaging modalities ranging from optical methods of second harmonic generation (SHG), polarized light microscopy (PLM), and optical coherence tomography (OCT) to the medical imaging approaches of ultrasound and magnetic resonance imaging (MRI). These methods have enabled scientists and clinicians to better understand the impact collagen structure has on the tumor environment, at both the bulk scale (density) and microscale (fibrillar structure) levels. We focus on imaging methods with the potential to both examine the collagen structure in as natural a state as possible and still be clinically amenable, with an emphasis on label-free strategies, exploiting intrinsic optical properties of collagen fibers.


Asunto(s)
Neoplasias , Microambiente Tumoral , Humanos , Colágenos Fibrilares/química , Diagnóstico por Imagen , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo
3.
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
4.
Nat Med ; 27(4): 632-639, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33649496

RESUMEN

Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson's disease (PD). Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons. A large body of experimental studies, including those in nonhuman primates, demonstrates that transplantation of fetal mesencephalic tissues improves motor symptoms in animals, which culminated in open-label and double-blinded clinical trials of fetal tissue transplantation for PD1. Unfortunately, the outcomes are mixed, primarily due to the undefined and unstandardized donor tissues1,2. Generation of induced pluripotent stem cells enables standardized and autologous transplantation therapy for PD. However, its efficacy, especially in primates, remains unclear. Here we show that over a 2-year period without immunosuppression, PD monkeys receiving autologous, but not allogenic, transplantation exhibited recovery from motor and depressive signs. These behavioral improvements were accompanied by robust grafts with extensive DA neuron axon growth as well as strong DA activity in positron emission tomography (PET). Mathematical modeling reveals correlations between the number of surviving DA neurons with PET signal intensity and behavior recovery regardless autologous or allogeneic transplant, suggesting a predictive power of PET and motor behaviors for surviving DA neuron number.


Asunto(s)
Conducta Animal , Depresión/complicaciones , Trasplante de Tejido Fetal , Actividad Motora , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Animales , Dopamina/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Inflamación/patología , Modelos Lineales , Macaca mulatta , Masculino , Mesencéfalo/trasplante , Ratones , Enfermedad de Parkinson/complicaciones , Tomografía de Emisión de Positrones , Trasplante Autólogo , Trasplante Homólogo , Tirosina 3-Monooxigenasa/metabolismo
5.
EJNMMI Res ; 10(1): 93, 2020 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-32761399

RESUMEN

PURPOSE: The aim of this study was to examine whether the translocator protein 18-kDa (TSPO) PET ligand [18F]FEPPA has the sensitivity for detecting changes in CD68-positive microglial/macrophage activation in hemiparkinsonian rhesus macaques treated with allogeneic grafts of induced pluripotent stem cell-derived midbrain dopaminergic neurons (iPSC-mDA). METHODS: In vivo positron emission tomography (PET) imaging with [18F]FEPPA was used in conjunction with postmortem CD68 immunostaining to evaluate neuroinflammation in the brains of hemiparkinsonian rhesus macaques (n = 6) that received allogeneic iPSC-mDA grafts in the putamen ipsilateral to MPTP administration. RESULTS: Based on assessment of radiotracer uptake and confirmed by visual inspection of the imaging data, nonhuman primates with allogeneic grafts showed increased [18F]FEPPA binding at the graft sites relative to the contralateral putamen. From PET asymmetry analysis of the images, the mean asymmetry index of the monkeys was AI = - 0.085 ± 0.018. Evaluation and scoring of CD68 immunoreactivity by an investigator blind to the treatment identified significantly more neuroinflammation in the grafted areas of the putamen compared to the contralateral putamen (p = 0.0004). [18F]FEPPA PET AI showed a positive correlation with CD68 immunoreactivity AI ratings in the monkeys (Spearman's ρ = 0.94; p = 0.005). CONCLUSION: These findings reveal that [18F]FEPPA PET is an effective marker for detecting increased CD68-positive microglial/macrophage activation and demonstrates sufficient sensitivity to detect changes in neuroinflammation in vivo following allogeneic cell engraftment.

6.
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
7.
J Neurosci ; 39(8): 1436-1444, 2019 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-30530859

RESUMEN

Dopamine (DA) levels in the striatum are increased by many therapeutic drugs, such as methylphenidate (MPH), which also alters behavioral and cognitive functions thought to be controlled by the PFC dose-dependently. We linked DA changes and functional connectivity (FC) using simultaneous [18F]fallypride PET and resting-state fMRI in awake male rhesus monkeys after oral administration of various doses of MPH. We found a negative correlation between [18F]fallypride nondisplaceable binding potential (BPND) and MPH dose in the head of the caudate (hCd), demonstrating increased extracellular DA resulting from MPH administration. The decreased BPND was negatively correlated with FC between the hCd and the PFC. Subsequent voxelwise analyses revealed negative correlations with FC between the hCd and the dorsolateral PFC, hippocampus, and precuneus. These results, showing that MPH-induced changes in DA levels in the hCd predict resting-state FC, shed light on a mechanism by which changes in striatal DA could influence function in the PFC.SIGNIFICANCE STATEMENT Dopamine transmission is thought to play an essential role in shaping large scale-neural networks that underlie cognitive functions. It is the target of therapeutic drugs, such as methylphenidate (Ritalin), which blocks the dopamine transporter, thereby increasing extracellular dopamine levels. Methylphenidate is used extensively to treat attention deficit hyperactivity disorder, even though its effects on cognitive functions and their underlying neural mechanisms are not well understood. To date, little is known about the link between changes in dopamine levels and changes in functional brain organization. Using simultaneous PET/MR imaging, we show that methylphenidate-induced changes in endogenous dopamine levels in the head of the caudate predict changes in resting-state functional connectivity between this structure and the prefrontal cortex, precuneus, and hippocampus.


Asunto(s)
Núcleo Caudado/fisiología , Conectoma , Inhibidores de Captación de Dopamina/farmacología , Corteza Prefrontal/fisiología , Animales , Benzamidas , Mapeo Encefálico , Núcleo Caudado/diagnóstico por imagen , Dopamina/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Relación Dosis-Respuesta a Droga , Radioisótopos de Flúor , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Metilfenidato/farmacología , Tomografía de Emisión de Positrones , Corteza Prefrontal/diagnóstico por imagen , Pirrolidinas , Radiofármacos
8.
PLoS One ; 13(6): e0197204, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29920524

RESUMEN

Dogs are commonly affected with cruciate ligament rupture (CR) and associated osteoarthritis (OA), and frequently develop a second contralateral CR. Platelet rich plasma (PRP) is a component of whole blood that contains numerous growth factors, which in combination with a collagen scaffold may act to promote bioenhanced primary repair of ligament. This study tested the hypothesis that treatment of partial stable CR stifles with an intra-articular collagen scaffold and PRP would decrease the disease progression, synovitis and risk of complete CR over a 12-month study period. We conducted a prospective cohort study of 29 client-owned dogs with an unstable stifle due to complete CR and stable contralateral stifle with partial CR. All dogs were treated with tibial plateau leveling osteotomy (TPLO) on the unstable stifle and a single intra-articular application of PRP-collagen in the stable partial CR stifle. Dogs were evaluated at the time of diagnosis, and at 10-weeks and 12-months after treatment. We evaluated correlation between both development of complete CR and time to complete CR with diagnostic tests including bilateral stifle radiographs, 3.0 Tesla magnetic resonance (MR) imaging, and bilateral stifle arthroscopy. Additionally, histologic evaluation of synovial biopsies, C-reactive protein (CRP) concentrations in serum and synovial fluid, and synovial total nucleated cell count, were determined. Results indicated that a single application of PRP-collagen in partial CR stifles of client owned dogs is not an effective disease-modifying therapy for the prevention of progression to complete CR. Radiographic effusion, arthroscopic evaluation of cranial cruciate ligament (CrCL) damage, and MR assessment of ligament fiber tearing in partial CR stifles correlated with progression to complete CR over the 12-month follow-up period. We determined that the best predictive model for development of complete CR in PRP-collagen treated partial CR stifles included variables from multiple diagnostic modalities.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Enfermedades de los Perros , Osteoartritis , Plasma Rico en Plaquetas , Andamios del Tejido , Animales , Ligamento Cruzado Anterior/metabolismo , Ligamento Cruzado Anterior/patología , Lesiones del Ligamento Cruzado Anterior/etiología , Lesiones del Ligamento Cruzado Anterior/metabolismo , Lesiones del Ligamento Cruzado Anterior/patología , Lesiones del Ligamento Cruzado Anterior/terapia , Proteína C-Reactiva/metabolismo , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/patología , Enfermedades de los Perros/terapia , Perros , Femenino , Masculino , Osteoartritis/complicaciones , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/terapia , Líquido Sinovial/metabolismo
9.
J Med Imaging (Bellingham) ; 5(1): 010901, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29392158

RESUMEN

Breast cancer is the most common cancer among women worldwide and ranks second in terms of overall cancer deaths. One of the difficulties associated with treating breast cancer is that it is a heterogeneous disease with variations in benign and pathologic tissue composition, which contributes to disease development, progression, and treatment response. Many of these phenotypes are uncharacterized and their presence is difficult to detect, in part due to the sparsity of methods to correlate information between the cellular microscale and the whole-breast macroscale. Quantitative multiscale imaging of the breast is an emerging field concerned with the development of imaging technology that can characterize anatomic, functional, and molecular information across different resolutions and fields of view. It involves a diverse collection of imaging modalities, which touch large sections of the breast imaging research community. Prospective studies have shown promising results, but there are several challenges, ranging from basic physics and engineering to data processing and quantification, that must be met to bring the field to maturity. This paper presents some of the challenges that investigators face, reviews currently used multiscale imaging methods for preclinical imaging, and discusses the potential of these methods for clinical breast imaging.

10.
Magn Reson Med ; 80(4): 1452-1466, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29446125

RESUMEN

PURPOSE: To develop a volumetric imaging technique with 0.8-mm isotropic resolution and 10-s/volume rate to detect and analyze breast lesions in a bilateral, dynamic, contrast-enhanced MRI exam. METHODS: A local low-rank temporal reconstruction approach that also uses parallel imaging and spatial compressed sensing was designed to create rapid volumetric frame rates during a contrast-enhanced breast exam (vastly undersampled isotropic projection [VIPR] spatial compressed sensing with temporal local low-rank [STELLR]). The dynamic-enhanced data are subtracted in k-space from static mask data to increase sparsity for the local low-rank approach to maximize temporal resolution. A T1 -weighted 3D radial trajectory (VIPR iterative decomposition with echo asymmetry and least squares estimation [IDEAL]) was modified to meet the data acquisition requirements of the STELLR approach. Additionally, the unsubtracted enhanced data are reconstructed using compressed sensing and IDEAL to provide high-resolution fat/water separation. The feasibility of the approach and the dual reconstruction methodology is demonstrated using a 16-channel breast coil and a 3T MR scanner in 6 patients. RESULTS: The STELLR temporal performance of subtracted data matched the expected temporal perfusion enhancement pattern in small and large vascular structures. Differential enhancement within heterogeneous lesions is demonstrated with corroboration from a basic reconstruction using a strict 10-second temporal footprint. Rapid acquisition, reliable fat suppression, and high spatiotemporal resolution are presented, despite significant data undersampling. CONCLUSION: The STELLR reconstruction approach of 3D radial sampling with mask subtraction provides a high-performance imaging technique for characterizing enhancing structures within the breast. It is capable of maintaining temporal fidelity, while visualizing breast lesions with high detail over a large FOV to include both breasts.


Asunto(s)
Mama/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Mama/diagnóstico por imagen , Medios de Contraste , Estudios de Factibilidad , Femenino , Humanos , Relación Señal-Ruido
11.
PLoS One ; 12(6): e0178086, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28575001

RESUMEN

Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging. We conducted a prospective cohort study of 29 client-owned dogs with an unstable stifle due to complete CR and stable contralateral stifle with partial CR. We evaluated correlation of stifle synovitis and CrCL fiber damage with diagnostic tests including bilateral stifle radiographs, 3.0 Tesla MR imaging, and bilateral stifle arthroscopy. Histologic grading and immunohistochemical staining for CD3+ T lymphocytes, TRAP+ activated macrophages and Factor VIII+ blood vessels in bilateral stifle synovial biopsies were also performed. Serum and synovial fluid concentrations of C-reactive protein (CRP) and carboxy-terminal telopeptide of type I collagen (ICTP), and synovial total nucleated cell count were determined. Synovitis was increased in complete CR stifles relative to partial CR stifles (P<0.0001), although total nucleated cell count in synovial fluid was increased in partial CR stifles (P<0.01). In partial CR stifles, we found that 3D Fast Spin Echo Cube CrCL signal intensity was correlated with histologic synovitis (SR = 0.50, P<0.01) and that radiographic OA was correlated with CrCL fiber damage assessed arthroscopically (SR = 0.61, P<0.001). Taken together, results of this study show that clinical diagnostic tests predict severity of stifle synovitis and cruciate ligament matrix damage in stable partial CR stifles. These data support use of client-owned dogs with unilateral complete CR and contralateral partial CR as a clinical trial model for investigation of disease-modifying therapy for partial CR.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior/veterinaria , Ligamento Cruzado Anterior/patología , Enfermedades de los Perros/patología , Rodilla de Cuadrúpedos/patología , Sinovitis/veterinaria , Animales , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/inmunología , Lesiones del Ligamento Cruzado Anterior/complicaciones , Lesiones del Ligamento Cruzado Anterior/inmunología , Lesiones del Ligamento Cruzado Anterior/patología , Artroscopía , Proteína C-Reactiva/análisis , Enfermedades de los Perros/inmunología , Perros , Femenino , Imagen por Resonancia Magnética , Masculino , Radiografía , Líquido Sinovial/inmunología , Sinovitis/complicaciones , Sinovitis/inmunología , Sinovitis/patología
12.
IEEE Trans Med Imaging ; 36(2): 527-537, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28113746

RESUMEN

We present MRiLab, a new comprehensive simulator for large-scale realistic MRI simulations on a regular PC equipped with a modern graphical processing unit (GPU). MRiLab combines realistic tissue modeling with numerical virtualization of an MRI system and scanning experiment to enable assessment of a broad range of MRI approaches including advanced quantitative MRI methods inferring microstructure on a sub-voxel level. A flexible representation of tissue microstructure is achieved in MRiLab by employing the generalized tissue model with multiple exchanging water and macromolecular proton pools rather than a system of independent proton isochromats typically used in previous simulators. The computational power needed for simulation of the biologically relevant tissue models in large 3D objects is gained using parallelized execution on GPU. Three simulated and one actual MRI experiments were performed to demonstrate the ability of the new simulator to accommodate a wide variety of voxel composition scenarios and demonstrate detrimental effects of simplified treatment of tissue micro-organization adapted in previous simulators. GPU execution allowed  âˆ¼ 200× improvement in computational speed over standard CPU. As a cross-platform, open-source, extensible environment for customizing virtual MRI experiments, MRiLab streamlines the development of new MRI methods, especially those aiming to infer quantitatively tissue composition and microstructure.


Asunto(s)
Imagen por Resonancia Magnética , Gráficos por Computador , Simulación por Computador
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.
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
15.
Vet J ; 209: 150-5, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26831152

RESUMEN

Estimation of cranial cruciate ligament (CrCL) structural properties in client-owned dogs with incipient cruciate rupture would be advantageous. The objective of this study was to determine whether magnetic resonance imaging (MRI) measurement of normal CrCL volume in an ex-vivo canine model predicts structural properties. Stifles from eight dogs underwent 3.0 Tesla 3D MRI. CrCL volume and normalized median grayscale values were determined using 3D Fast Spin Echo (FSE) Cube and Vastly under-sampled Isotropic PRojection (VIPR)-alternative repetition time (aTR) sequences. Stifles were then mechanically tested. After joint laxity testing, CrCL structural properties were determined, including displacement at yield, yield load, load to failure, and stiffness. Yield load and load to failure (R(2)=0.56, P <0.01) were correlated with CrCL volume determined by VIPR-aTR. Yield load was also correlated with CrCL volume determined by 3D FSE Cube (R(2)=0.32, P <0.05). Structural properties were not related to median grayscale values. Joint laxity and CrCL stiffness were not related to MRI parameters, but displacement at yield load was related to CrCL volume for both sequences during testing (R(2)>0.57, P <0.005). In conclusion, 3D MRI offers a predictive method for estimating canine CrCL structural properties. 3D MRI may be useful for monitoring CrCL properties in clinical trials.


Asunto(s)
Ligamento Cruzado Anterior/diagnóstico por imagen , Rodilla de Cuadrúpedos/diagnóstico por imagen , Animales , Ligamento Cruzado Anterior/fisiología , Fenómenos Biomecánicos , Perros , Imagenología Tridimensional/veterinaria , Imagen por Resonancia Magnética/veterinaria , Rodilla de Cuadrúpedos/fisiología
16.
Magn Reson Med ; 75(4): 1423-33, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25959974

RESUMEN

PURPOSE: To study the effects of magnetization transfer (MT) on multicomponent T2 parameters obtained using mcDESPOT in macromolecule-rich tissues and to propose a new method called mcRISE to correct MT-induced biases. METHODS: The two-pool mcDESPOT model was modified by the addition of an exchanging macromolecule proton pool to model the MT effect in cartilage. The mcRISE acquisition scheme was developed to provide sensitivity to all pools. An incremental fitting was applied to estimate MT and relaxometry parameters with minimized coupling. The interaction between MT and relaxometry parameters, efficacy of MT correction, and feasibility of mcRISE in vivo were investigated in simulations and in healthy volunteers. RESULTS: The MT effect caused significant errors in multicomponent T1/T2 values and in fast-relaxing water fraction fF , which is consistent with previous experimental observations. fF increased significantly with macromolecule content if MT was ignored. mcRISE resulted in a multifold reduction of MT biases and yielded decoupled multicomponent T1/T2 relaxometry and quantitative MT parameters. CONCLUSION: mcRISE is an efficient approach for correcting MT biases in multicomponent relaxometry based on steady state sequences. Improved specificity of mcRISE may help to elucidate the sources of the previously described high sensitivity of noncorrected mcDESPOT parameters to disease-related changes in cartilage and the brain.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Adulto , Cartílago Articular/diagnóstico por imagen , Simulación por Computador , Humanos , Rodilla/diagnóstico por imagen , Masculino
17.
Magn Reson Med ; 75(3): 1269-77, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25946145

RESUMEN

PURPOSE: Chemical shift based fat/water decomposition methods such as IDEAL are frequently used in challenging imaging environments with large B0 inhomogeneity. However, they do not account for the signal modulations introduced by a balanced steady state free precession (bSSFP) acquisition. Here we demonstrate improved performance when the bSSFP frequency response is properly incorporated into the multipeak spectral fat model used in the decomposition process. THEORY AND METHODS: Balanced SSFP allows for rapid imaging but also introduces a characteristic frequency response featuring periodic nulls and pass bands. Fat spectral components in adjacent pass bands will experience bulk phase offsets and magnitude modulations that change the expected constructive and destructive interference between the fat spectral components. A bSSFP signal model was incorporated into the fat/water decomposition process and used to generate images of a fat phantom, and bilateral breast and knee images in four normal volunteers at 1.5 Tesla. RESULTS: Incorporation of the bSSFP signal model into the decomposition process improved the performance of the fat/water decomposition. CONCLUSION: Incorporation of this model allows rapid bSSFP imaging sequences to use robust fat/water decomposition methods such as IDEAL. While only one set of imaging parameters were presented, the method is compatible with any field strength or repetition time.


Asunto(s)
Tejido Adiposo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Procesamiento de Señales Asistido por Computador , Agua/química , Tejido Adiposo/química , Algoritmos , Mama/diagnóstico por imagen , Femenino , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Fantasmas de Imagen
18.
J Magn Reson Imaging ; 43(5): 1140-7, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26435385

RESUMEN

PURPOSE: To investigate the use of a three-pool model to account for the confounding effects of synovial fluid on multicomponent T2 analysis of articular cartilage using Multicomponent Driven Equilibrium Single Shot Observation of T1 and T2 (mcDESPOT). MATERIALS AND METHODS: mcDESPOT was performed on the knee of eight asymptomatic volunteers and eight patients with osteoarthritis at 3.0T with multicomponent T2 maps created using the two-pool model and a three-pool model containing a nonexchanging synovial fluid water pool. The fraction of the fast-relaxing water component (FF ) and the T2 relaxation times for the fast-relaxing (T2F ) and slow-relaxing (T2S ) water components were measured in the superficial and deep layers of patellar cartilage using the two-pool and three-pool models in asymptomatic volunteers and patients with osteoarthritis and were compared using Wilcoxon signed rank tests. RESULTS: Within the superficial layer of patellar cartilage, FF was 22.5% and 25.6% for asymptomatic volunteers and 21.3% and 22.8% for patients with osteoarthritis when using the two-pool and three-pool models, respectively, while T2S was 73.9 msec and 62.0 msec for asymptomatic volunteers and 72.0 msec and 63.1 msec for patients with osteoarthritis when using the two-pool and three-pool models, respectively. For both asymptomatic volunteers and patients with osteoarthritis, the two-pool model provided significantly (P < 0.05) lower FF and higher T2S than the three-pool model, likely due to the effects of synovial fluid partial volume averaging. CONCLUSION: The effects of partial volume averaging between superficial cartilage and synovial fluid may result in biased multicomponent T2 measurements that can be corrected using an mcDESPOT three-pool model containing a nonexchanging synovial fluid water pool.


Asunto(s)
Cartílago Articular/patología , Imagen por Resonancia Magnética , Osteoartritis/fisiopatología , Líquido Sinovial/química , Adulto , Cartílago Articular/diagnóstico por imagen , Femenino , Voluntarios Sanos , Humanos , Interpretación de Imagen Asistida por Computador , Procesamiento de Imagen Asistido por Computador , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Osteoartritis/patología , Rótula/diagnóstico por imagen , Rótula/patología , Reproducibilidad de los Resultados , Agua/química
19.
Radiology ; 277(2): 477-88, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26024307

RESUMEN

PURPOSE: To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. MATERIALS AND METHODS: This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2(Single)), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (F(F)) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. RESULTS: Higher cartilage T2(Single) (P < .001), lower cartilage F(F) (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2(Single) and F(F) remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with F(F) than with T2(Single) for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis. CONCLUSION: Patients with osteoarthritis of the knee had significantly higher cartilage T2(Single) and significantly lower cartilage F(F) than did asymptomatic volunteers, and receiver operating characteristic analysis results suggested that F(F) may allow greater diagnostic performance than that with T2(Single) for distinguishing between normal and degenerative cartilage.


Asunto(s)
Cartílago Articular/patología , Imagen por Resonancia Magnética/métodos , Osteoartritis de la Rodilla/patología , Adulto , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados
20.
J Magn Reson Imaging ; 42(5): 1321-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25847733

RESUMEN

PURPOSE: To compare multicomponent T2 parameters of menisci measured using Multicomponent Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and osteoarthritis (OA) patients with intact and torn menisci. MATERIALS AND METHODS: The prospective study was performed with Institutional Review Board approval and with all subjects signing written informed consent. mcDESPOT was performed on the knee joint of 12 asymptomatic volunteers and 14 patients with knee OA. Single-component T2 relaxation time (T2Single ), T2 relaxation time of the fast relaxing water component (T2F ), and the slow relaxing water component (T2S ), and fraction of the fast relaxing water component (FF ) of the medial and lateral menisci were measured. Multivariate linear regression models were used to compare mcDESPOT parameters between normal menisci in asymptomatic volunteers, intact menisci in OA patients, and torn menisci in OA patients with adjustment for differences in age between subjects. RESULTS: The mean mcDESPOT parameters for normal menisci in asymptomatic volunteers, intact menisci in OA patients, and torn menisci in OA patients were respectively 16.1 msec, 18.8 msec, and 22.7 msec for T2Single ; 9.0 msec, 10.0 msec, and 11.1 msec for T2F ; 24.4 msec, 27.7 msec, and 31.4 msec for T2S ; and 34%, 32%, 27% for FF . There were significant differences (P < 0.05) in T2Single , T2F , T2S , and FF between the three groups of menisci. CONCLUSION: The menisci of OA patients had significantly higher T2Single , T2F , and T2S and significantly lower FF than normal menisci in asymptomatic volunteers with greater changes in multicomponent T2 parameters noted in torn than intact menisci in OA patients.


Asunto(s)
Cartílago Articular/patología , Traumatismos de la Rodilla/patología , Imagen por Resonancia Magnética , Meniscos Tibiales/patología , Osteoartritis de la Rodilla/patología , Adulto , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados
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