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1.
AJR Am J Roentgenol ; 221(2): 228-239, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36919879

RESUMEN

BACKGROUND. PET/CT with 18F-fluoroestradiol (FES) (FDA-approved in 2020) depicts tissues expressing estrogen receptor (ER). Invasive lobular carcinoma (ILC) is commonly ER positive. OBJECTIVE. The primary aim of this study was to assess the frequency with which sites of histologically proven ILC have abnormal uptake on FES PET/CT. METHODS. This prospective single-center pilot study, conducted from December 2020 to August 2021, enrolled patients with histologically confirmed ILC to undergo FES PET/CT; patients optionally underwent FDG PET/CT. Two nuclear radiologists assessed FES PET/CT and FDG PET/CT studies for abnormal uptake corresponding to known ILC sites at enrollment and for additional sites of abnormal uptake, resolving differences by consensus. The primary endpoint was percentage of known ILC sites showing abnormal FES uptake. The alternative to the null hypothesis was that more than 60% of sites would have abnormal FES uptake, exceeding the percentage of ILC with abnormal FDG uptake described in prior literature. A sample size of 24 biopsied lesions was preselected to provide 81% power for the alternative hypothesis (one-sided α = .10). Findings on FES PET/CT and FDG PET/CT were summarized for additional secondary endpoints. RESULTS. The final analysis included 17 patients (mean age, 59.1 ± 13.2 years) with 25 sites of histologically confirmed ILC at enrollment (22 breast lesions, two axillary lymph nodes, one distant metastasis). FES PET/CT showed abnormal uptake in 22 of 25 (88%) lesions, sufficient to reject the null hypothesis (p = .002). Thirteen patients underwent FDG PET/CT. Four of 23 (17%) sites of histologically confirmed ILC, including additional sites detected and confirmed after enrollment, were identified with FES PET/CT only, and 1 of 23 (4%) was identified only with FDG PET/CT (p = .18). FES PET/CT depicted additional lesions not detected with standard-of-care evaluation in 4 of 17 (24%) patients (two contralateral breast cancers and two metastatic axillary lymph nodes, all with subsequent histologic confirmation). Use of FES PET/CT resulted in changes in clinical stage with respect to standard-of-care evaluation in 3 of 17 (18%) patients. CONCLUSION. The primary endpoint of the trial was met. The frequency of abnormal FES uptake among sites of histologically known ILC was found to be to be significantly greater than 60%. CLINICAL IMPACT. This pilot study shows a potential role of FES PET/CT in evaluation of patients with ILC. TRIAL REGISTRATION. ClinicalTrials.gov NCT04252859.


Asunto(s)
Neoplasias de la Mama , Carcinoma Lobular , Humanos , Persona de Mediana Edad , Anciano , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/patología , Proyectos Piloto , Fluorodesoxiglucosa F18 , Estudios Prospectivos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Tomografía de Emisión de Positrones/métodos , Estradiol
2.
Magn Reson Med ; 83(6): 1930-1939, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31677194

RESUMEN

PURPOSE: It is important to identify populations that may be vulnerable to the brain deposition of gadolinium (Gd) from MRI contrast agents. At intervals from 24 hours to 6 weeks following injection of a linear Gd contrast agent, the brain, blood and bone content of Gd were compared between control rats and those with experimental endotoxin-induced sepsis that results in neuroinflammation and blood-brain barrier disruption. METHODS: Male rats were injected intraperitoneally with 10 mg/kg lipopolysaccharide. Control animals received no injection. Twenty-four hours later, 0.2 mmol/kg of gadobenate dimeglumine was injected intravenously. Brain, blood, and bone Gd levels were measured at 24 hours, 1 week, 3 weeks, and 6 weeks by inductively coupled plasma mass spectroscopy. RESULTS: Blood Gd decreased rapidly between 24 hours and 1 week, and thereafter was undetectable, with no significant difference between lipopolysaccharide and control rats. Brain levels of Gd were significantly higher (4.29-2.36-fold) and bone levels slightly higher (1.35-1.11-fold) in lipopolysaccharide than control rats at all time points with significant retention at 6 weeks. CONCLUSION: Experimental sepsis results in significantly higher deposition of Gd in the brain and bone in rats. While blood Gd clears rapidly, brain and bone retained substantial Gd even at 6 weeks following contrast injection.


Asunto(s)
Compuestos Organometálicos , Sepsis , Animales , Encéfalo/diagnóstico por imagen , Medios de Contraste , Gadolinio , Gadolinio DTPA , Imagen por Resonancia Magnética , Masculino , Ratas , Sepsis/diagnóstico por imagen
4.
J Magn Reson Imaging ; 43(2): 391-7, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26174884

RESUMEN

PURPOSE: To evaluate the performance of an edge-based registration technique in correcting for respiratory motion artifacts in magnetic resonance renographic (MRR) data and to examine the efficiency of a semiautomatic software package in processing renographic data from a cohort of clinical patients. MATERIALS AND METHODS: The developed software incorporates an image-registration algorithm based on the generalized Hough transform of edge maps. It was used to estimate glomerular filtration rate (GFR), renal plasma flow (RPF), and mean transit time (MTT) from 36 patients who underwent free-breathing MRR at 3T using saturation-recovery turbo-FLASH. The processing time required for each patient was recorded. Renal parameter estimates and model-fitting residues from the software were compared to those from a previously reported technique. Interreader variability in the software was quantified by the standard deviation of parameter estimates among three readers. GFR estimates from our software were also compared to a reference standard from nuclear medicine. RESULTS: The time taken to process one patient's data with the software averaged 12 ± 4 minutes. The applied image registration effectively reduced motion artifacts in dynamic images by providing renal tracer-retention curves with significantly smaller fitting residues (P < 0.01) than unregistered data or data registered by the previously reported technique. Interreader variability was less than 10% for all parameters. GFR estimates from the proposed method showed greater concordance with reference values (P < 0.05). CONCLUSION: These results suggest that the proposed software can process MRR data efficiently and accurately. Its incorporated registration technique based on the generalized Hough transform effectively reduces respiratory motion artifacts in free-breathing renographic acquisitions.


Asunto(s)
Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Enfermedades Renales/patología , Riñón/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Artefactos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados
5.
Urol Case Rep ; 47: 102352, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36866336

RESUMEN

75-year-old patient with cochlear implant diagnosed with very low risk prostate cancer (PSA 6.44 ng/mL, and Grade Group 1 (left apical core)) managed on Active Surveillance (AS). After four years monitoring on AS, PSA was observed to increase to 10.84 and patient was reevaluated for disease progression. Due to cochlear implant, multiparametric MRI was not an imaging option and patient was referred for piflufolastat F 18-PET/CT. In addition to previously identified left sided lesion, tracer uptake was observed within the posterior transition and peripheral zone of the right lobe of the prostate, which ultimately confirmed disease progression on targeted biopsy.

6.
Clin Nucl Med ; 47(1): 56-58, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34269726

RESUMEN

ABSTRACT: Pineal region metastases are very rare, occurring in 0.4% to 3.8% of patients with solid tumors and most frequently arise from a lung cancer primary tumor. We present a case of a 67-year-old man with a gastric well-differentiated neuroendocrine tumor (NET) metastatic to the pineal gland identified on 68Ga-DOTATATE PET/CT imaging followed by MRI confirmation. To our knowledge, this is the third NET case to be reported in the literature with such presentation and first case to be described on 68Ga-DOTATATE PET/CT. A case of metastatic bronchial NET as well as a case of metastatic esophageal NET to the pineal gland were reported previously.


Asunto(s)
Tumor Carcinoide , Tumores Neuroendocrinos , Compuestos Organometálicos , Glándula Pineal , Anciano , Tumor Carcinoide/diagnóstico por imagen , Humanos , Masculino , Glándula Pineal/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Cintigrafía
7.
Cancers (Basel) ; 14(11)2022 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-35681647

RESUMEN

PET-CT is an advanced imaging modality with many oncologic applications, including staging, assessment of response to therapy, restaging and longitudinal surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, and the potential pitfalls and nuances that characterize these applications. In the third of these review articles, key tumor-specific clinical information and representative PET-CT images are provided to outline the role that PET-CT plays in the management of patients with gastrointestinal malignancies. The focus is on the use of 18F fluorodeoxyglucose (FDG), rather than on research radiopharmaceuticals under development. Many different types of gastrointestinal tumors exist, both pediatric and adult. A discussion of the role of FDG PET-CT for all of these is beyond the scope of this review. Rather, this article focuses on the most common adult gastrointestinal malignancies that may be encountered in clinical practice. The information provided here will provide information outlining the appropriate role of PET-CT in the clinical management of patients with gastrointestinal malignancies for healthcare professionals caring for adult cancer patients. It also addresses the nuances and provides interpretive guidance related to PET-CT for imaging providers, including radiologists, nuclear medicine physicians and their trainees.

8.
Cancers (Basel) ; 14(11)2022 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-35681669

RESUMEN

Positron emission tomography combined with x-ray computed tomography (PET-CT) is an advanced imaging modality with oncologic applications that include staging, therapy assessment, restaging, and surveillance. This six-part series of review articles provides practical information to providers and imaging professionals regarding the best use of PET-CT for the more common adult malignancies. The second article of this series addresses primary thoracic malignancy and breast cancer. For primary thoracic malignancy, the focus will be on lung cancer, malignant pleural mesothelioma, thymoma, and thymic carcinoma, with an emphasis on the use of FDG PET-CT. For breast cancer, the various histologic subtypes will be addressed, and will include 18F fluorodeoxyglucose (FDG), recently Food and Drug Administration (FDA)-approved 18F-fluoroestradiol (FES), and 18F sodium fluoride (NaF). The pitfalls and nuances of PET-CT in breast and primary thoracic malignancies and the imaging features that distinguish between subcategories of these tumors are addressed. This review will serve as a resource for the appropriate roles and limitations of PET-CT in the clinical management of patients with breast and primary thoracic malignancies for healthcare professionals caring for adult patients with these cancers. It also serves as a practical guide for imaging providers, including radiologists, nuclear medicine physicians, and their trainees.

9.
Cancers (Basel) ; 14(11)2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35681709

RESUMEN

PET-CT is an advanced imaging modality with many oncologic applications, including staging, assessment of response to therapy, restaging, and longitudinal surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, and the potential pitfalls and nuances that characterize these applications. In addition, key tumor-specific clinical information and representative PET-CT images are provided to outline the role that PET-CT plays in the management of oncology patients. Hundreds of different types of tumors exist, both pediatric and adult. A discussion of the role of FDG PET for all of these is beyond the scope of this review. Rather, this series of articles focuses on the most common adult malignancies that may be encountered in clinical practice. It also focuses on FDA-approved and clinically available radiopharmaceuticals, rather than research tracers or those requiring a local cyclotron. The fifth review article in this series focuses on PET-CT imaging in head and neck tumors, as well as brain tumors. Common normal variants, key anatomic features, and benign mimics of these tumors are reviewed. The goal of this review article is to provide the imaging professional with guidance in the interpretation of PET-CT for the more common head and neck malignancies and neuro oncology, and to inform the referring providers so that they can have realistic expectations of the value and limitations of PET-CT for the specific type of tumor being addressed.

10.
Cancers (Basel) ; 14(12)2022 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-35740501

RESUMEN

PET-CT is an advanced imaging modality with many oncologic applications, including staging, therapeutic assessment, restaging and surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, the potential pitfalls and nuances that characterize these applications, and guidelines for image interpretation. Tumor-specific clinical information and representative PET-CT images are provided. The current, sixth article in this series addresses PET-CT in an evaluation of aggressive cutaneous malignancies, sarcomas and neuroendocrine tumors. A discussion of the role of FDG PET for all types of tumors in these categories is beyond the scope of this review. Rather, this article focuses on the most common malignancies in adult patients encountered in clinical practice. It also focuses on Food and Drug Agency (FDA)-approved and clinically available radiopharmaceuticals rather than research tracers or those requiring a local cyclotron. This information will serve as a guide to primary providers for the appropriate role of PET-CT in managing patients with cutaneous malignancies, sarcomas and neuroendocrine tumors. The nuances of PET-CT interpretation as a practical guide for imaging providers, including radiologists, nuclear medicine physicians and their trainees, are also addressed.

11.
Cancers (Basel) ; 14(12)2022 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-35740665

RESUMEN

Concurrently acquired positron emission tomography and computed tomography (PET-CT) is an advanced imaging modality with diverse oncologic applications, including staging, therapeutic assessment, restaging and longitudinal surveillance. This series of six review articles focuses on providing practical information to providers and imaging professionals regarding the best use and interpretative strategies of PET-CT for oncologic indications in adult patients. In this fourth article of the series, the more common gynecological and adult genitourinary malignancies encountered in clinical practice are addressed, with an emphasis on Food and Drug Administration (FDA)-approved and clinically available radiopharmaceuticals. The advent of new FDA-approved radiopharmaceuticals for prostate cancer imaging has revolutionized PET-CT imaging in this important disease, and these are addressed in this report. However, [18F]F-fluoro-2-deoxy-d-glucose (FDG) remains the mainstay for PET-CT imaging of gynecologic and many other genitourinary malignancies. This information will serve as a guide for the appropriate role of PET-CT in the clinical management of gynecologic and genitourinary cancer patients for health care professionals caring for adult cancer patients. It also addresses the nuances and provides guidance in the accurate interpretation of FDG PET-CT in gynecological and genitourinary malignancies for imaging providers, including radiologists, nuclear medicine physicians and their trainees.

12.
Cancers (Basel) ; 14(23)2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36497423

RESUMEN

PET-CT is an advanced imaging modality with many oncologic applications, including staging, assessment of response to therapy, restaging and evaluation of suspected recurrence. The goal of this 6-part series of review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for the more common adult malignancies. In the first article of this series, hematologic malignancies are addressed. The classification of these malignancies will be outlined, with the disclaimer that the classification of lymphomas is constantly evolving. Critical applications, potential pitfalls, and nuances of PET-CT imaging in hematologic malignancies and imaging features of the major categories of these tumors are addressed. Issues of clinical importance that must be reported by the imaging professionals are outlined. The focus of this article is on [18F] fluorodeoxyglucose (FDG), rather that research tracers or those requiring a local cyclotron. This information will serve as a resource for the appropriate role and limitations of PET-CT in the clinical management of patients with hematological malignancy for health care professionals caring for adult patients with hematologic malignancies. It also serves as a practical guide for imaging providers, including radiologists, nuclear medicine physicians and their trainees.

13.
Tomography ; 7(4): 581-605, 2021 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-34698290

RESUMEN

Dedicated multi-slice single-photon emission computed tomography/computed tomography (SPECT/CT) cameras have become widely available and are becoming a mainstay of clinical practice. The integration of SPECT and CT allow for precise anatomic location of scintigraphic findings. Fusion imaging with SPECT/CT can improve both sensitivity and specificity by reducing equivocal interpretation in comparison to planar scintigraphy or SPECT alone. This review article addresses the technique, basic science principles, and applications of integrated SPECT/CT in the evaluation of musculoskeletal pathology.


Asunto(s)
Sistema Musculoesquelético , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Cintigrafía , Sensibilidad y Especificidad , Tomografía Computarizada de Emisión de Fotón Único/métodos
14.
Geroscience ; 43(2): 563-578, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33846885

RESUMEN

Rapamycin (RAPA) is found to have neuro-protective properties in various neuroinflammatory pathologies, including brain aging. With magnetic resonance imaging (MRI) techniques, we investigated the effect of RAPA in a lipopolysaccharide (LPS)-induced inflammaging model in rat brains. Rats were exposed to saline (control), or LPS alone or LPS combined with RAPA treatment (via food over 6 weeks). Arterial spin labeling (ASL) perfusion imaging was used to measure relative cerebral blood flow (rCBF). MR spectroscopy (MRS) was used to measure brain metabolite levels. Contrast-enhanced MRI (CE-MRI) was used to assess blood-brain barrier (BBB) permeability. Immunohistochemistry (IHC) was used to confirm neuroinflammation. RAPA restored NF-κB and HIF-1α to normal levels. RAPA was able to significantly restore rCBF in the cerebral cortex post-LPS exposure (p < 0.05), but not in the hippocampus. In the hippocampus, RAPA was able to restore total creatine (Cr) acutely, and N-acetyl aspartate (NAA) at 6 weeks, post-LPS. Myo-inositol (Myo-Ins) levels were found to decrease with RAPA treatment acutely post-LPS. RAPA was also able to significantly restore the BBB acutely post-LPS in both the cortex and hippocampus (p < 0.05 for both). RAPA was found to increase the percent change in BOLD signal in the cortex at 3 weeks, and in the hippocampus at 6 weeks post-LPS, compared to LPS alone. RAPA treatment also restored the neuronal and macro-vascular marker, EphB2, back to normal levels. These results indicate that RAPA may play an important therapeutic role in inhibiting neuroinflammation by normalizing brain vascularity, BBB, and some brain metabolites, and has a high translational capability.


Asunto(s)
Barrera Hematoencefálica , Sirolimus , Animales , Encéfalo , Circulación Cerebrovascular , Imagen por Resonancia Magnética , Ratas , Sirolimus/farmacología
15.
Am J Nucl Med Mol Imaging ; 11(3): 196-206, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34234998

RESUMEN

This study evaluates F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) semi-quantitative analysis as biomarker of tumor aggressiveness and predictor of survival in patients with primary brain tumors. Semi-quantitative analyses (SUVmax, SUVmean) were derived from FDG PET images in 78 patients with suspected recurrence of primary brain tumors based on MRI. SUVmax and the ratio of lesion SUVmax to the SUVmean of contralateral white matter (SUVmax/WM) were measured. A one-way Analysis of Variance (ANOVA), Kaplan-Meier analyses and the log rank test for evaluating statistical significance were utilized. There was statistical significance for time between FDG-PET and patient death. There was a significant difference with respect to FDG-PET time to death between patients with glioblastoma and patients with anaplastic oligodendroglioma, oligodendroglioma, and other histological subtypes. There is significant correlation with SUVmax/WM and patient survival following FDG-PET when a cut-point ratio of 1.90 is used. A 1.90 cut-point ratio of SUVmax/WM was associated with a difference in survival. GBM was associated with a significant difference in terms of reduced survival following FDG PET compared to most other histological sub-types. These results may inform current treatment and counseling strategies for patients with primary brain tumors.

16.
J Nucl Med ; 50(8): 1205-13, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19617339

RESUMEN

UNLABELLED: The purpose of this study was to compare optimized whole-body (WB) and dedicated high-resolution contrast-enhanced PET/CT protocols and contrast enhanced CT in the preoperative staging of primary squamous cell carcinoma of the head and neck. METHODS: A total of 44 patients with clinically M0 squamous cell carcinoma of the head and neck underwent primary tumor resection and neck dissection within 6 wk of diagnostic imaging. Imaging consisted of a standard WB PET/CT protocol without intravenous contrast enhancement, followed by a high-resolution dedicated head and neck (HN) PET/CT protocol, which included diagnostic-quality contrast-enhanced CT (CECT). Imaging results were compared with histopathology. A 5-point scale was used to designate primary tumor localization and the presence of lymph node metastasis on a per-patient and per-level basis. For cervical nodes, receiver-operating-characteristic curves were generated to determine the differences in performance between the WB and HN PET/CT protocols and CECT. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for primary tumor and cervical nodes. RESULTS: No statistical difference was observed between WB and HN PET/CT protocols, both of which significantly outperformed CECT, in the evaluation of the primary tumor. The performance of the HN PET/CT protocol was superior to that of the WB PET/CT in the detection of cervical node metastases, achieving statistical significance on a per-level basis and approaching significance on a per-patient basis, with the greatest advantage in the detection of small positive lymph nodes (<15 mm). No significant difference was observed between the WB PET/CT protocol and CECT in nodal staging, either on a per-patient or on a per-level basis. CONCLUSION: The primary advantage of the dedicated HN PET/CT protocol over the WB protocol or CECT in the staging of head and neck cancer is in the detection of small lymph node metastases.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/secundario , Neoplasias de Cabeza y Cuello/diagnóstico , Aumento de la Imagen/métodos , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Imagen de Cuerpo Entero/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/cirugía , Medios de Contraste , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Preoperatorios , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Técnica de Sustracción
17.
Geroscience ; 41(4): 483-494, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31478121

RESUMEN

Lipopolysaccharide (LPS)-induced encephalopathy induces neuroinflammation. Long-term neuroinflammation is associated with aging and subsequent cognitive impairment (CI). We treated rats that had LPS-induced neuroinflammation with OKN-007, with an anti-inflammatory agent currently considered an anti-cancer investigational new drug in clinical trials for glioblastoma (GBM). Contrast-enhanced magnetic resonance imaging (MRI) (CE-MRI), perfusion MRI, and MR spectroscopy were used as methods to assess long-term (up to 6 weeks post-LPS) alterations in blood-brain barrier (BBB) permeability, microvascularity, and metabolism, respectively, and the therapeutic effect of OKN-007. A free radical-targeted molecular MRI approach was also used to detect the effect of OKN-007 on brain free radical levels at 24 h and 1 week post-LPS injection. OKN-007 was able to reduce BBB permeability in the cerebral cortex and hippocampus at 1 week post-LPS using CE-MRI. OKN-007 was able to restore vascular perfusion rates by reducing LPS-induced increased relative cerebral blood flow (rCBF) in the cortex and hippocampus regions at all time points studied (1, 3, and 6 weeks post-LPS). OKN-007 was also able to restore LPS-induced brain metabolite depletions. NAA/Cho, Cr/Cho, and Myo-Ins/Cho metabolite ratios at 1, 3, and 6 weeks post-LPS were all restored to normal levels following OKN-007 treatment. OKN-007 also reduced LPS-induced free radical levels at 24 h and 1 week post-LPS, as detected by free radical-targeted MRI. LPS-exposed rats were compared with saline-treated controls and LPS + OKN-007-treated animals. We clearly demonstrated that OKN-007 restores LPS-induced BBB dysfunction, impaired vascularity, and decreased brain metabolites, all long-term neuroinflammatory indicators, as well as decreases free radicals in a LPS-induced neuroinflammation model. OKN-007 should be considered an anti-inflammatory agent for age-associated neuroinflammation.


Asunto(s)
Antiinflamatorios/farmacología , Bencenosulfonatos/farmacología , Encefalopatías/tratamiento farmacológico , Corteza Cerebral/diagnóstico por imagen , Circulación Cerebrovascular , Hipocampo/diagnóstico por imagen , Iminas/farmacología , Animales , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encefalopatías/inducido químicamente , Corteza Cerebral/metabolismo , Colina/metabolismo , Medios de Contraste , Creatina/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Inositol/metabolismo , Lipopolisacáridos/toxicidad , Imagen por Resonancia Magnética/métodos , Imagen de Perfusión , Ratas Sprague-Dawley , Flujo Sanguíneo Regional
18.
Geroscience ; 41(4): 467-481, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31473912

RESUMEN

Sepsis is a severe systemic inflammatory response to infection associated with acute and chronic neurocognitive consequences, including an increased risk of later-life dementia. In a lipopolysaccharide-induced rat sepsis model, we have demonstrated neuroinflammation, cortical amyloid-beta plaque deposition, and increased whole brain levels of phosphorylated tau. Hippocampal abnormalities, particularly those of the dentate gyrus, are seen in Alzheimer's disease and age-related memory loss. The focus of this study was to determine whether Aß plaques and phosphorylated tau aggregates occur in the hippocampus as a consequence of lipopolysaccharide administration, and whether behavioral abnormalities related to the hippocampus, particularly the dentate gyrus, can be demonstrated. Male Sprague Dawley rats received an intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin. Control animals received a saline injection. Seven days post injection, Aß plaques and phosphorylated tau in the hippocampus were quantified following immunostaining. Behavioral tests that have previously been shown to result in specific deficits in dentate gyrus-lesioned rats were administered. Lipopolysaccharide treatment results in the deposition of beta amyloid plaques and intracellular phosphorylated tau in the hippocampus, including the dorsal dentate gyrus. Lipopolysaccharide treatment resulted in behavioral deficits attributable to the dorsal dentate gyrus, including episodic-like memory function that primarily involves spatial, contextual, and temporal orientation and integration. Lipopolysaccharide administration results in hippocampal deposition of amyloid-beta plaques and intracellular phosphorylated tau and results in specific behavioral deficits attributable to the dorsal dentate gyrus. These findings, if persistent, could provide a basis for the higher rate of dementia in longitudinal studies of sepsis survivors.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Lipopolisacáridos/toxicidad , Placa Amiloide/metabolismo , Proteínas tau/metabolismo , Animales , Conducta Animal , Giro Dentado/metabolismo , Modelos Animales de Enfermedad , Fosforilación , Ratas Sprague-Dawley , Sepsis/complicaciones , Conducta Espacial
19.
Am J Nucl Med Mol Imaging ; 8(2): 86-99, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29755842

RESUMEN

Amyloid beta (Aß) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aß may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aß production are associated with Aß plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS). Brain and blood levels of IL-1ß, IL-6, and TNFα and cortical microglial density were measured in LPS-injected and control animals. Soluble brain Aß and p-tau were compared and Aß plaques were quantified and characterized. Brain uptake of [18F]flutemetamol was measured by phosphor imaging. LPS endotoxemia resulted in elevations of cytokines in blood and brain. Microglial density was increased in LPS-treated rats relative to controls. LPS resulted in increased soluble Aß and in p-tau levels in whole brain. Progressive increases in morphologically-diffuse Aß plaques occurred throughout the interval of observation (to 7-9 days post LPS). LPS endotoxemia resulted in increased [18F]flutemetamol in the cortex and increased cortex: white matter ratios of activity. In conclusion, LPS endotoxemia causes neuroinflammation, increased soluble Aß and Aß diffuse plaques in the brain. Aß PET tracers may inform this neuropathology. Increased p-tau in the brain of LPS treated animals suggests that downstream consequences of Aß plaque formation may occur. Further mechanistic and neurocognitive studies to understand the causes and consequences of LPS-induced neuropathology are warranted.

20.
AJR Am J Roentgenol ; 188(3): 866-73, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17312080

RESUMEN

OBJECTIVE: The purpose of this article is to discuss and show examples of the PET appearance of common brain abnormalities that radiologists encounter when interpreting whole-body 18F-FDG PET examinations of cancer patients. CONCLUSION: Knowledge of the PET appearance of various brain abnormalities can yield diagnostically relevant information in cancer patients. Detection of brain abnormalities on whole-body PET often requires adjusting window settings to reduce the intensity of normal brain FDG activity. Often, close correlation of PET/CT and MRI with clinical history offers the most complete radiologic diagnosis.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Aumento de la Imagen/métodos , Tomografía de Emisión de Positrones/métodos , Humanos , Radiofármacos
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