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1.
Nucleic Acids Res ; 52(13): 7740-7760, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38932701

RESUMEN

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic inhibition of OC2 suppresses lineage plasticity reprogramming induced by the AR signaling inhibitor enzalutamide. These results demonstrate that OC2 activation promotes a range of drug resistance mechanisms associated with treatment-emergent lineage variation in PC and support enhanced efforts to therapeutically target OC2 as a means of suppressing treatment-resistant disease.


Asunto(s)
Adenocarcinoma , Benzamidas , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Nitrilos , Neoplasias de la Próstata , Receptores Androgénicos , Receptores de Glucocorticoides , Masculino , Humanos , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/tratamiento farmacológico , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Benzamidas/farmacología , Línea Celular Tumoral , Nitrilos/farmacología , Feniltiohidantoína/farmacología , Feniltiohidantoína/análogos & derivados , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Epigénesis Genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/tratamiento farmacológico , Animales , Linaje de la Célula/genética , Ratones
2.
MAGMA ; 37(3): 383-396, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38922525

RESUMEN

OBJECT: To review recent advances of artificial intelligence (AI) in enhancing the efficiency and throughput of the MRI acquisition workflow in neuroimaging, including planning, sequence design, and correction of acquisition artifacts. MATERIALS AND METHODS: A comprehensive analysis was conducted on recent AI-based methods in neuro MRI acquisition. The study focused on key technological advances, their impact on clinical practice, and potential risks associated with these methods. RESULTS: The findings indicate that AI-based algorithms have a substantial positive impact on the MRI acquisition process, improving both efficiency and throughput. Specific algorithms were identified as particularly effective in optimizing acquisition steps, with reported improvements in workflow efficiency. DISCUSSION: The review highlights the transformative potential of AI in neuro MRI acquisition, emphasizing the technological advances and clinical benefits. However, it also discusses potential risks and challenges, suggesting areas for future research to mitigate these concerns and further enhance AI integration in MRI acquisition.


Asunto(s)
Algoritmos , Inteligencia Artificial , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Neuroimagen , Humanos , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Artefactos , Encéfalo/diagnóstico por imagen , Flujo de Trabajo , Interpretación de Imagen Asistida por Computador/métodos
3.
Molecules ; 29(12)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38930864

RESUMEN

The low light absorption efficiency has seriously hindered the application of two-dimensional transition metal dichalcogenide (TMDC) nanosheets in the field of optoelectronic devices. Various approaches have been used to improve the performance of TMDC nanosheets. Preparation of one-dimensional TMDC nanoscrolls in combination with photoactive materials has been a promising method to improve their properties recently. In this work, we report a facile method to enhance the optoelectronic performance of TMDC nanoscrolls by wrapping the photoactive organic dye rhodamine (R6G) into them. After R6G molecules were deposited on monolayer TMDC nanosheets by the solution method, the R6G/MoS2 nanoscrolls with lengths up to hundreds of microns were prepared in a short time by dropping a mixture of ammonia and ethanol solution on the R6G/MoS2 nanosheets. The as-obtained R6G/MoS2 nanoscrolls were well characterized by optical microscopy, atomic force microscopy, Raman spectroscopy, and transmission electron microscopy to prove the encapsulation of R6G. There are multiple type II heterojunction interfaces in the R6G/MoS2 nanoscrolls, which can promote the generation of photo-induced carriers and the following electron-hole separation. The separated electrons were transported rapidly along the axial direction of the R6G/MoS2 nanoscrolls, which greatly improves the efficiency of light absorption and photoresponse. Under the irradiation of an incident 405 nm laser, the photoresponsivity, carrier mobility, external quantum efficiency, and detectivity of R6G/MoS2 nanoscrolls were enhanced to 66.07 A/W, 132.93 cm2V-1s-1, 20,261%, and 1.25 × 1012 cm·Hz1/2W-1, which are four orders of magnitude higher than those of monolayer MoS2 nanosheets. Our work indicates that the R6G/TMDC hybrid nanoscrolls could be promising materials for high-performance optoelectronic devices.

4.
Hum Brain Mapp ; 44(6): 2209-2223, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-36629336

RESUMEN

Quantitative assessment of brain myelination has gained attention for both research and diagnosis of neurological diseases. However, conventional pulse sequences cannot directly acquire the myelin-proton signals due to its extremely short T2 and T2* values. To obtain the myelin-proton signals, dedicated short T2 acquisition techniques, such as ultrashort echo time (UTE) imaging, have been introduced. However, it remains challenging to isolate the myelin-proton signals from tissues with longer T2. In this article, we extended our previous two-dimensional ultrashort echo time magnetic resonance fingerprinting (UTE-MRF) with dual-echo acquisition to three dimensional (3D). Given a relatively low proton density (PD) of myelin-proton, we utilized Cramér-Rao Lower Bound to encode myelin-proton with the maximal SNR efficiency for optimizing the MR fingerprinting design, in order to improve the sensitivity of the sequence to myelin-proton. In addition, with a second echo of approximately 3 ms, myelin-water component can be also captured. A myelin-tissue (myelin-proton and myelin-water) fraction mapping can be thus calculated. The optimized 3D UTE-MRF with dual-echo acquisition is tested in simulations, physical phantom and in vivo studies of both healthy subjects and multiple sclerosis patients. The results suggest that the rapidly decayed myelin-proton and myelin-water signal can be depicted with UTE signals of our method at clinically relevant resolution (1.8 mm isotropic) in 15 min. With its good sensitivity to myelin loss in multiple sclerosis patients demonstrated, our method for the whole brain myelin-tissue fraction mapping in clinical friendly scan time has the potential for routine clinical imaging.


Asunto(s)
Esclerosis Múltiple , Vaina de Mielina , Humanos , Protones , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Agua , Espectroscopía de Resonancia Magnética , Imagenología Tridimensional/métodos
5.
Magn Reson Med ; 88(1): 239-253, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35253922

RESUMEN

PURPOSE: To introduce a computationally efficient approach to optimizing the data acquisition parameters of MR Fingerprinting experiments with the Cramér-Rao bound. METHODS: This paper presents a new approach to the optimal experimental design (OED) problem for MR Fingerprinting, which leverages an early observation that the optimized data acquisition parameters of MR Fingerprinting experiments are highly structured. Specifically, the proposed approach captures the desired structure by representing the sequences of data acquisition parameters with a special class of piecewise polynomials known as B-splines. This incorporates low-dimensional spline subspace constraints into the OED problem, which significantly reduces the search space of the problem, thereby improving the computational efficiency. With the rich B-spline representations, the proposed approach also allows for incorporating prior knowledge on the structure of different acquisition parameters, which facilitates the experimental design. RESULTS: The effectiveness of the proposed approach was evaluated using numerical simulations, phantom experiments, and in vivo experiments. The proposed approach achieves a two-order-of-magnitude improvement of the computational efficiency over the state-of-the-art approaches, while providing a comparable signal-to-noise ratio efficiency benefit. It enables an optimal experimental design problem for MR Fingerprinting with a typical acquisition length to be solved in approximately 1 min. CONCLUSIONS: The proposed approach significantly improves the computational efficiency of the optimal experimental design for MR Fingerprinting, which enhances its practical utility for a variety of quantitative MRI applications.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Proyectos de Investigación , Algoritmos , Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Fantasmas de Imagen , Relación Señal-Ruido
6.
Magn Reson Med ; 88(2): 633-650, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35436357

RESUMEN

PURPOSE: To rapidly obtain high resolution T2 , T2 *, and quantitative susceptibility mapping (QSM) source separation maps with whole-brain coverage and high geometric fidelity. METHODS: We propose Blip Up-Down Acquisition for Spin And Gradient Echo imaging (BUDA-SAGE), an efficient EPI sequence for quantitative mapping. The acquisition includes multiple T2 *-, T2 '-, and T2 -weighted contrasts. We alternate the phase-encoding polarities across the interleaved shots in this multi-shot navigator-free acquisition. A field map estimated from interim reconstructions was incorporated into the joint multi-shot EPI reconstruction with a structured low rank constraint to eliminate distortion. A self-supervised neural network (NN), MR-Self2Self (MR-S2S), was used to perform denoising to boost SNR. Using Slider encoding allowed us to reach 1 mm isotropic resolution by performing super-resolution reconstruction on volumes acquired with 2 mm slice thickness. Quantitative T2 (=1/R2 ) and T2 * (=1/R2 *) maps were obtained using Bloch dictionary matching on the reconstructed echoes. QSM was estimated using nonlinear dipole inversion on the gradient echoes. Starting from the estimated R2 /R2 * maps, R2 ' information was derived and used in source separation QSM reconstruction, which provided additional para- and dia-magnetic susceptibility maps. RESULTS: In vivo results demonstrate the ability of BUDA-SAGE to provide whole-brain, distortion-free, high-resolution, multi-contrast images and quantitative T2 /T2 * maps, as well as yielding para- and dia-magnetic susceptibility maps. Estimated quantitative maps showed comparable values to conventional mapping methods in phantom and in vivo measurements. CONCLUSION: BUDA-SAGE acquisition with self-supervised denoising and Slider encoding enables rapid, distortion-free, whole-brain T2 /T2 * mapping at 1 mm isotropic resolution under 90 s.


Asunto(s)
Mapeo Encefálico , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Fenómenos Magnéticos , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen
7.
Ann Diagn Pathol ; 58: 151923, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35180608

RESUMEN

Yolk sac differentiation occurs in somatic neoplasms of the gastrointestinal and gynecologic tracts; it has rarely been reported in urothelial carcinoma. Here, we report three cases of yolk sac differentiation in sarcomatoid urothelial carcinoma. The epithelioid component of the sarcomatoid urothelial carcinoma showed divergent differentiation, including squamous, conventional glandular, small cell carcinoma, and yolk sac components. The sarcomatoid component showed malignant spindle cells admixed with focal chondroid and rhabdoid elements. In all three cases, the yolk sac areas were admixed with the sarcomatoid component and showed a glandular pattern, with vacuolated, eosinophilic cytoplasm. These areas were positive for SALL4, variably positive for glypican 3 and AFP, and negative for the conventional urothelial markers GATA3, p63, and 34ßE12. Yolk sac differentiation is an extremely rare occurrence in sarcomatoid urothelial carcinoma.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Biomarcadores de Tumor , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patología , Femenino , Humanos , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patología , Saco Vitelino/patología
8.
J Urol ; 206(1): 80-87, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33683939

RESUMEN

PURPOSE: This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368). MATERIALS AND METHODS: Eligible patients had a Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored. RESULTS: The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor. CONCLUSIONS: Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor <5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.


Asunto(s)
Acetato de Abiraterona/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos/uso terapéutico , Leuprolida/uso terapéutico , Prednisona/uso terapéutico , Prostatectomía , Neoplasias de la Próstata/cirugía , Tiohidantoínas/uso terapéutico , Anciano , Terapia Combinada , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Neoplasias de la Próstata/patología , Medición de Riesgo , Resultado del Tratamiento
9.
Prostate ; 80(2): 113-132, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31825540

RESUMEN

INTRODUCTION: The 2019 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Prostate Cancer Research: The Next Generation," was held 20 to 23 June, 2019, in Los Angeles, California. METHODS: The CHPCA Meeting is an annual conference held by the Prostate Cancer Foundation, that is uniquely structured to stimulate intense discussion surrounding topics most critical to accelerating prostate cancer research and the discovery of new life-extending treatments for patients. The 7th Annual CHPCA Meeting was attended by 86 investigators and concentrated on many of the most promising new treatment opportunities and next-generation research technologies. RESULTS: The topics of focus at the meeting included: new treatment strategies and novel agents for targeted therapies and precision medicine, new treatment strategies that may synergize with checkpoint immunotherapy, next-generation technologies that visualize tumor microenvironment (TME) and molecular pathology in situ, multi-omics and tumor heterogeneity using single cells, 3D and TME models, and the role of extracellular vesicles in cancer and their potential as biomarkers. DISCUSSION: This meeting report provides a comprehensive summary of the talks and discussions held at the 2019 CHPCA Meeting, for the purpose of globally disseminating this knowledge and ultimately accelerating new treatments and diagnostics for patients with prostate cancer.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Animales , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo
10.
Mod Pathol ; 32(8): 1158-1167, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30914763

RESUMEN

Rapid histological assessment of large areas of prostate tissue is required for many intraoperative consultation scenarios such as margin evaluation. Nonlinear microscopy (NLM) enables imaging of large (whole mount) specimens without freezing or cryotoming. This study demonstrates rapid histological imaging of unsectioned prostate cancer surgical specimens using nonlinear microscopy and compares features of prostate pathology to standard paraffin embedded H&E histology. Fresh or formalin fixed specimens were stained in 2.5 min with fluorescent nuclear and stromal dyes. Nonlinear microscopy images of unsectioned tissues were generated by nonlinear (two-photon) excitation of the fluorophores, where fluorescence is only emitted from tissue at the microscope focus, avoiding the need for physical sectioning. The images were displayed in real time using a color scale similar to H&E, then tissues were processed for standard paraffin embedded H&E histology. Seventy nonlinear microscopy and corresponding paraffin H&E images of fresh and fixed prostate specimens (15 cancer, 55 benign) from 24 patients were read by genitourinary pathologists to assess if nonlinear microscopy could achieve an equivalent evaluation to paraffin embedded H&E histology. Differences between nonlinear microscopy images and paraffin H&E slides, including cytoplasmic color and stromal density, were observed, however nonlinear microscopy images could be interpreted with minimal training. Nonlinear microscopy enabled visualization of benign, atrophic and hyperplastic glands and stroma, ejaculatory ducts, vasculature and inflammatory changes. Nonlinear microscopy enabled identification of typical and variants of adenocarcinoma, as well as Gleason patterns. Perineural invasion and extraprostatic extension could also be assessed. Nonlinear microscopy images closely resemble paraffin H&E slides and enable rapid assessment of normal prostate architecture, benign conditions, and carcinoma in freshly excised and fixed specimens. Nonlinear microscopy can image large regions of tissue, equivalent to multiple frozen section tissue blocks, within minutes because cryotoming/microtoming are not required, making it a promising technique for intraoperative consultation.


Asunto(s)
Colorantes , Eosina Amarillenta-(YS) , Hematoxilina , Microscopía de Fluorescencia por Excitación Multifotónica , Próstata/patología , Neoplasias de la Próstata/patología , Coloración y Etiquetado , Humanos , Cuidados Intraoperatorios , Masculino , Márgenes de Escisión , Proyectos Piloto , Valor Predictivo de las Pruebas , Próstata/cirugía , Prostatectomía , Neoplasias de la Próstata/cirugía , Reproducibilidad de los Resultados , Factores de Tiempo , Flujo de Trabajo
11.
Magn Reson Med ; 82(1): 289-301, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30883867

RESUMEN

PURPOSE: To develop a fast, sub-millimeter 3D magnetic resonance fingerprinting (MRF) technique for whole-brain quantitative scans. METHODS: An acquisition trajectory based on multi-axis spiral projection imaging (maSPI) was implemented for 3D MRF with steady-state precession and slab excitation. By appropriately assigning the in-plane and through-plane rotations of spiral interleaves in a novel acquisition scheme, an maSPI-based acquisition was implemented, and the total acquisition time was reduced by up to a factor of 8 compared to stack-of-spiral (SOS)-based acquisition. A sliding-window method was also used to further reduce the required number of time points for a faster acquisition. The experiments were conducted both on a phantom and in vivo. RESULTS: The results from the phantom measurements with the proposed and gold standard methods were consistent with a good linear correlation and an R2 value approaching 0.99. The in vivo experiments achieved whole-brain parametric maps with isotropic resolutions of 1 mm and 0.8 mm in 5.0 and 6.0 min, respectively, with potential for further acceleration. An in vivo experiment with intentionally moving subjects demonstrated that the maSPI scheme largely outperforms the SOS scheme in terms of robustness to head motion. CONCLUSION: 3D MRF with an maSPI acquisition scheme enables fast and robust scans for high-resolution parametric mapping.


Asunto(s)
Encéfalo/diagnóstico por imagen , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Humanos , Fantasmas de Imagen
12.
Magn Reson Med ; 82(4): 1359-1372, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31131911

RESUMEN

PURPOSE: To demonstrate an ultrashort echo time magnetic resonance fingerprinting (UTE-MRF) method that allows quantifying relaxation times for muscle and bone in the musculoskeletal system and generating bone enhanced images that mimic CT scans. METHODS: A fast imaging steady-state free precession MRF sequence with half pulse excitation and half projection readout was designed to sample fast T2 decay signals. Varying echo time (TE) of a sinusoidal pattern was applied to enhance sensitivity for tissues with short and ultrashort T2 values. The performance of UTE-MRF was evaluated via simulations, phantom, and in vivo experiments. RESULTS: A minimal TE of 0.05 ms was achieved. Simulations indicated the sinusoidal TE sampling increased T2 quantification accuracy in the cortical bone and tendon but had little impact on long T2 muscle quantifications. For the rubber phantom, the averaged relaxometries from UTE-MRF (T1 = 162 ms and T2 = 1.07 ms) compared well with the gold standard (T1 = 190 ms and T2∗ = 1.03 ms). For the long T2 agarose phantom, the linear regression slope between UTE-MRF and gold standard was 1.07 (R2 = 0.991) for T1 and 1.04 (R2 = 0.994) for T2 . In vivo experiments showed the detection of the cortical bone (averaged T2 = 1.0 ms) and Achilles tendon (averaged T2 = 15 ms). Scalp structures from the bone enhanced image show high similarity with CT. CONCLUSION: The UTE-MRF with sinusoidal TEs can simultaneously quantify T1 , T2 , proton density, and B0 in long, short, even ultrashort T2 musculoskeletal structures. Bone enhanced images can be achieved in the brain with UTE-MRF.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Simulación por Computador , Hueso Cortical/diagnóstico por imagen , Humanos , Pierna/diagnóstico por imagen , Fantasmas de Imagen , Tendones/diagnóstico por imagen
13.
Nucleic Acids Res ; 45(7): 3738-3751, 2017 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-28062857

RESUMEN

P-TEFb (CDK9/cyclin T) plays a central role in androgen receptor (AR)-mediated transactivation by phosphorylating both RNA polymerase 2 complex proteins and AR at S81. CDK9 dephosphorylation mobilizes P-TEFb from an inhibitory 7SK ribonucleoprotein complex, but mechanisms targeting phosphatases to P-TEFb are unclear. We show that AR recruits protein phosphatase 1α (PP1α), resulting in P-TEFb mobilization and CDK9-mediated AR S81 phosphorylation. This increased pS81 enhances p300 recruitment, histone acetylation, BRD4 binding and subsequent further recruitment of P-TEFb, generating a positive feedback loop that sustains transcription. AR S81 is also phosphorylated by CDK1, and blocking basal CDK1-mediated S81 phosphorylation markedly suppresses AR activity and initiation of this positive feedback loop. Finally, androgen-independent AR activity in castration-resistant prostate cancer (CRPC) cells is driven by increased CDK1-mediated S81 phosphorylation. Collectively these findings reveal a mechanism involving PP1α, CDK9 and CDK1 that is used by AR to initiate and sustain P-TEFb activity, which may be exploited to drive AR in CRPC.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Factor B de Elongación Transcripcional Positiva/metabolismo , Neoplasias de la Próstata/genética , Proteína Fosfatasa 1/metabolismo , Receptores Androgénicos/metabolismo , Antagonistas de Receptores Androgénicos/farmacología , Proteína Quinasa CDC2/metabolismo , Línea Celular Tumoral , Cromatina/metabolismo , Quinasa 9 Dependiente de la Ciclina/metabolismo , Retroalimentación Fisiológica , Humanos , Masculino , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/metabolismo , Activación Transcripcional
14.
Radiology ; 288(3): 804-812, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29916782

RESUMEN

Purpose To improve diagnosis of hippocampal sclerosis (HS) in patients with mesial temporal lobe epilepsy (MTLE) by using MR fingerprinting and compare with visual assessment of T1- and T2-weighted MR images. Materials and Methods For this prospective study performed between April and November 2016, T1 and T2 maps were obtained and tissue segmentation performed in consecutive patients with drug-resistant MTLE with unilateral or bilateral HS. T1 and T2 maps were compared between 33 patients with MTLE (23 women and 10 men; mean age, 32.6 years; age range, 16-60 years) and 30 healthy participants (20 women and 10 men; mean age, 28.8 years; age range, 18-40 years). Differences in individual bilateral hippocampi were compared by using a Wilcoxon signed rank test, whereas the Wilcoxon rank-sum test was used for difference analysis between healthy control participants and patients with MTLE. Results The diagnosis rate (ie, ratio of HS diagnosed on the basis of a 2.5-minute MR fingerprinting examination compared with standard methods: MRI, electroencephalography, and PET) was 32 of 33 (96.9%; 95% confidence interval: 84.9%, 100%), reflecting improved accuracy of diagnosis (P = 1.92 × 10-12) over routine MR examinations that had a diagnostic rate of 23 of 33 (69.7%; 95% confidence interval: 51.5%, 81.6%). The comparison between atrophic and normal-appearing hippocampus in 33 patients with MTLE and healthy control participants demonstrated that both T1 and T2 values in HS lesions were higher than those of normal hippocampal tissue of healthy participants (T1: 1361 msec ± 85 vs 1249 msec ± 59, respectively; T2: 135 msec ± 15 vs 104 msec ± 9, respectively; P < .0001). Conclusion MR fingerprinting allowed for multiparametric mapping of temporal lobe within 2.5 minutes and helped to identify lesions suspicious for HS in patients with MTLE with improved accuracy.


Asunto(s)
Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico por imagen , Adolescente , Adulto , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Adulto Joven
15.
Magn Reson Med ; 79(2): 933-942, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28411394

RESUMEN

PURPOSE: This article introduces a constrained imaging method based on low-rank and subspace modeling to improve the accuracy and speed of MR fingerprinting (MRF). THEORY AND METHODS: A new model-based imaging method is developed for MRF to reconstruct high-quality time-series images and accurate tissue parameter maps (e.g., T1 , T2 , and spin density maps). Specifically, the proposed method exploits low-rank approximations of MRF time-series images, and further enforces temporal subspace constraints to capture magnetization dynamics. This allows the time-series image reconstruction problem to be formulated as a simple linear least-squares problem, which enables efficient computation. After image reconstruction, tissue parameter maps are estimated via dictionary-based pattern matching, as in the conventional approach. RESULTS: The effectiveness of the proposed method was evaluated with in vivo experiments. Compared with the conventional MRF reconstruction, the proposed method reconstructs time-series images with significantly reduced aliasing artifacts and noise contamination. Although the conventional approach exhibits some robustness to these corruptions, the improved time-series image reconstruction in turn provides more accurate tissue parameter maps. The improvement is pronounced especially when the acquisition time becomes short. CONCLUSIONS: The proposed method significantly improves the accuracy of MRF, and also reduces data acquisition time. Magn Reson Med 79:933-942, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Algoritmos , Encéfalo/diagnóstico por imagen , Humanos , Fantasmas de Imagen
16.
Neuroimage ; 155: 577-586, 2017 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-28435102

RESUMEN

T2* weighted 3D Gradient Echo (GRE) acquisition is the main sequence used for Susceptibility Weighted Imaging (SWI) and Quantitative Susceptibility Mapping (QSM). These applications require a long echo time (TE) to build up phase contrast, requiring a long repetition time (TR), and leading to excessively lengthy scans. The long TE acquisition creates a significant amount of unused time within each TR, which can be utilized for either multi-echo sampling or additional image encoding with the echo-shift technique. The latter leads to significant saving in acquisition time while retaining the desired phase and T2* contrast. In this work, we introduce the Simultaneous Time Interleaved MultiSlice (STIMS) echo-shift technique, which mitigates slab boundary artifacts by interleaving comb-shaped slice groups with Simultaneous MultiSlice (SMS) excitation. This enjoys the same SNR benefit of 3D signal averaging as previously introduced multi-slab version, where each slab group is sub-resolved with kz phase encoding. Further, we combine SMS echo-shift with Compressed Sensing (CS) Wave acceleration, which enhances Wave-CAIPI acquisition/reconstruction with random undersampling and sparsity prior. STIMS and CS-Wave combination thus yields up to 45-fold acceleration over conventional full encoding, allowing a 15sec full-brain acquisition with 1.5 mm isotropic resolution at long TE of 39 ms at 3T. In addition to utilizing empty sequence time due to long TE, STIMS is a general concept that could exploit gaps due to e.g. inversion modules in magnetization-prepared rapid gradient-echo (MPRAGE) and fluid attenuated inversion recovery (FLAIR) sequences.


Asunto(s)
Encéfalo/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Adulto , Humanos , Masculino
17.
Magn Reson Med ; 78(4): 1579-1588, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-27851871

RESUMEN

PURPOSE: To develop a method for accelerated and robust MR fingerprinting (MRF) with improved image reconstruction and parameter matching processes. THEORY AND METHODS: A sliding-window (SW) strategy was applied to MRF, in which signal and dictionary matching was conducted between fingerprints consisting of mixed-contrast image series reconstructed from consecutive data frames segmented by a sliding window, and a precalculated mixed-contrast dictionary. The effectiveness and performance of this new method, dubbed SW-MRF, was evaluated in both phantom and in vivo. Error quantifications were conducted on results obtained with various settings of SW reconstruction parameters. RESULTS: Compared with the original MRF strategy, the results of both phantom and in vivo experiments demonstrate that the proposed SW-MRF strategy either provided similar accuracy with reduced acquisition time, or improved accuracy with equal acquisition time. Parametric maps of T1 , T2 , and proton density of comparable quality could be achieved with a two-fold or more reduction in acquisition time. The effect of sliding-window width on dictionary sensitivity was also estimated. CONCLUSION: The novel SW-MRF recovers high quality image frames from highly undersampled MRF data, which enables more robust dictionary matching with reduced numbers of data frames. This time efficiency may facilitate MRF applications in time-critical clinical settings. Magn Reson Med 78:1579-1588, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Algoritmos , Encéfalo/diagnóstico por imagen , Humanos , Fantasmas de Imagen
18.
Magn Reson Med ; 78(5): 1870-1876, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28019022

RESUMEN

PURPOSE: The purpose of this study is to accelerate an MR fingerprinting (MRF) acquisition by using a simultaneous multislice method. METHODS: A multiband radiofrequency (RF) pulse was designed to excite two slices with different flip angles and phases. The signals of two slices were driven to be as orthogonal as possible. The mixed and undersampled MRF signal was matched to two dictionaries to retrieve T1 and T2 maps of each slice. Quantitative results from the proposed method were validated with the gold-standard spin echo methods in a phantom. T1 and T2 maps of in vivo human brain from two simultaneously acquired slices were also compared to the results of fast imaging with steady-state precession based MRF method (MRF-FISP) with a single-band RF excitation. RESULTS: The phantom results showed that the simultaneous multislice imaging MRF-FISP method quantified the relaxation properties accurately compared to the gold-standard spin echo methods. T1 and T2 values of in vivo brain from the proposed method also matched the results from the normal MRF-FISP acquisition. CONCLUSION: T1 and T2 values can be quantified at a multiband acceleration factor of two using our proposed acquisition even in a single-channel receive coil. Further acceleration could be achieved by combining this method with parallel imaging or iterative reconstruction. Magn Reson Med 78:1870-1876, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Algoritmos , Encéfalo/diagnóstico por imagen , Humanos , Fantasmas de Imagen
19.
Magn Reson Med ; 77(5): 1966-1974, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27220881

RESUMEN

PURPOSE: To develop a reconstruction method to improve SMS-MRF, in which slice acceleration is used in conjunction with highly undersampled in-plane acceleration to speed up MRF acquisition. METHODS: In this work two methods are employed to efficiently perform the simultaneous multislice magnetic resonance fingerprinting (SMS-MRF) data acquisition and the direct-spiral slice-GRAPPA (ds-SG) reconstruction. First, the lengthy training data acquisition is shortened by employing the through-time/through-k-space approach, in which similar k-space locations within and across spiral interleaves are grouped and are associated with a single set of kernel. Second, inversion recovery preparation (IR prepped), variable flip angle (FA), and repetition time (TR) are used for the acquisition of the training data, to increase signal variation and to improve the conditioning of the kernel fitting. RESULTS: The grouping of k-space locations enables a large reduction in the number of kernels required, and the IR-prepped training data with variable FA and TR provide improved ds-SG kernels and reconstruction performance. With direct-spiral slice-GRAPPA, tissue parameter maps comparable to that of conventional MRF were obtained at multiband (MB) = 3 acceleration using t-blipped SMS-MRF acquisition with 32-channel head coil at 3 Tesla (T). CONCLUSIONS: The proposed reconstruction scheme allows MB = 3 accelerated SMS-MRF imaging with high-quality T1 , T2 , and off-resonance maps, and can be used to significantly shorten MRF acquisition and aid in its adoption in neuro-scientific and clinical settings. Magn Reson Med 77:1966-1974, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Espectroscopía de Resonancia Magnética/métodos , Procesamiento de Señales Asistido por Computador , Aceleración , Algoritmos , Artefactos , Encéfalo/patología , Imagen Eco-Planar/métodos , Humanos , Aumento de la Imagen/métodos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional/métodos , Programas Informáticos
20.
Neuroimage ; 125: 1131-1141, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26277773

RESUMEN

Three-dimensional gradient echo (GRE) is the main workhorse sequence used for susceptibility weighted imaging (SWI), quantitative susceptibility mapping (QSM), and susceptibility tensor imaging (STI). Achieving optimal phase signal-to-noise ratio requires late echo times, thus necessitating a long repetition time (TR). Combined with the large encoding burden of whole-brain coverage with high resolution, this leads to increased scan time. Further, the dipole kernel relating the tissue phase to the underlying susceptibility distribution undersamples the frequency content of the susceptibility map. Scans at multiple head orientations along with calculation of susceptibility through multi-orientation sampling (COSMOS) are one way to effectively mitigate this issue. Additionally, STI requires a minimum of 6 head orientations to solve for the independent tensor elements in each voxel. The requirements of high-resolution imaging with long TR at multiple orientations substantially lengthen the acquisition of COSMOS and STI. The goal of this work is to dramatically speed up susceptibility mapping at multiple head orientations. We demonstrate highly efficient acquisition using 3D-GRE with Wave-CAIPI and dramatically reduce the acquisition time of these protocols. Using R=15-fold acceleration with Wave-CAIPI permits acquisition per head orientation in 90s at 1.1mm isotropic resolution, and 5:35min at 0.5mm isotropic resolution. Since Wave-CAIPI fully harnesses the 3D spatial encoding capability of receive arrays, the maximum g-factor noise amplification remains below 1.30 at 3T and 1.12 at 7T. This allows a 30-min exam for STI with 12 orientations, thus paving the way to its clinical application.


Asunto(s)
Mapeo Encefálico/métodos , Imagen de Difusión Tensora/métodos , Interpretación de Imagen Asistida por Computador/métodos , Adulto , Humanos , Aumento de la Imagen/métodos , Imagenología Tridimensional/métodos , Masculino
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