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1.
Proc Natl Acad Sci U S A ; 121(31): e2403212121, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39042688

RESUMEN

Some mental health problems such as depression and anxiety are more common in females, while others such as autism and attention deficit/hyperactivity (AD/H) are more common in males. However, the neurobiological origins of these sex differences are poorly understood. Animal studies have shown substantial sex differences in neuronal and glial cell structure, while human brain imaging studies have shown only small differences, which largely reflect overall body and brain size. Advanced diffusion MRI techniques can be used to examine intracellular, extracellular, and free water signal contributions and provide unique insights into microscopic cellular structure. However, the extent to which sex differences exist in these metrics of subcortical gray matter structures implicated in psychiatric disorders is not known. Here, we show large sex-related differences in microstructure in subcortical regions, including the hippocampus, thalamus, and nucleus accumbens in a large sample of young adults. Unlike conventional T1-weighted structural imaging, large sex differences remained after adjustment for age and brain volume. Further, diffusion metrics in the thalamus and amygdala were associated with depression, anxiety, AD/H, and antisocial personality problems. Diffusion MRI may provide mechanistic insights into the origin of sex differences in behavior and mental health over the life course and help to bridge the gap between findings from experimental, epidemiological, and clinical mental health research.


Asunto(s)
Encéfalo , Caracteres Sexuales , Humanos , Femenino , Masculino , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Salud Mental , Adulto Joven , Imagen de Difusión por Resonancia Magnética , Adolescente , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Tálamo/diagnóstico por imagen , Núcleo Accumbens/diagnóstico por imagen , Depresión/diagnóstico por imagen , Depresión/patología , Ansiedad/diagnóstico por imagen
2.
Behav Genet ; 53(3): 208-218, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37129746

RESUMEN

Using baseline (ages 9-10) and two-year follow-up (ages 11-12) data from monozygotic and dizygotic twins enrolled in the longitudinal Adolescent Brain Cognitive DevelopmentSM Study, we investigated the genetic and environmental contributions to microstructure and volume of nine subcortical gray matter regions. Microstructure was assessed using diffusion MRI data analyzed using restriction spectrum imaging (RSI) and diffusion tensor imaging (DTI) models. The highest heritability estimates (estimate [95% confidence interval]) for microstructure were found using the RSI model in the pallidum (baseline: 0.859 [0.818, 0.889], follow-up: 0.835 [0.787, 0.871]), putamen (baseline: 0.859 [0.819, 0.889], follow-up: 0.874 [0.838, 0.902]), and thalamus (baseline: 0.855 [0.814, 0.887], follow-up: 0.819 [0.769, 0.857]). For volumes the corresponding regions were the caudate (baseline: 0.831 [0.688, 0.992], follow-up: 0.848 [0.701, 1.011]) and putamen (baseline: 0.906 [0.875, 0.914], follow-up: 0.906 [0.885, 0.923]). The subcortical regions displayed high genetic stability (rA = 0.743-1.000) across time and exhibited unique environmental correlations (rE = 0.194-0.610). Individual differences in both gray matter microstructure and volumes can be largely explained by additive genetic effects in this sample.


Asunto(s)
Imagen de Difusión Tensora , Sustancia Gris , Adolescente , Humanos , Niño , Imagen de Difusión Tensora/métodos , Encéfalo , Gemelos Dicigóticos/genética , Cognición , Imagen por Resonancia Magnética
3.
Radiology ; 299(1): E187-E192, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33399509

RESUMEN

Severe acute respiratory syndrome coronavirus 2 has spread across the world since December 2019, infecting 100 million and killing millions. The impact on health care institutions during the coronavirus disease 2019 pandemic has been considerable, with exhaustion of institutional and personal protective equipment resources during local outbreaks and crushing financial consequences for many institutions. Establishing adaptive principles of leadership is necessary during crises, fostering quick decision-making and workflow modifications, while a rapid review of data must determine necessary course corrections. This report describes concepts of crisis leadership teams that can help maximize their effectiveness during the current and future pandemics.


Asunto(s)
Comités Consultivos , COVID-19/diagnóstico , COVID-19/terapia , Liderazgo , Servicio de Radiología en Hospital/organización & administración , Humanos , América del Norte , SARS-CoV-2 , Sociedades Médicas
4.
J Neurooncol ; 155(2): 117-124, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34601657

RESUMEN

PURPOSE: Pre-clinical evidence suggests bevacizumab (BV) depletes the GBM peri-vascular cancer-stem cell niche. This phase I/II study assesses the safety and efficacy of repeated doses of superselective intra-arterial cerebral infusion (SIACI) of BV after blood-brain barrier disruption (BBBD). METHODS: Date of surgery was day 0. Evaluated patients received repeated SIACI bevacizumab (15 mg/kg) with BBBD at days 30 ± 7, 120 ± 7, and 210 ± 7 along with 6 weeks of standard chemoradiation. Response assessment in neuro-oncology criteria and the Kaplan-Meier product-limit method was used to evaluate progression free and overall survival (PFS and OS, respectively). RESULTS: Twenty-three patients with a median age of 60.5 years (SD = 12.6; 24.7-78.3) were included. Isocitrate dehydrogenase mutation was found in 1/23 (4%) patients. MGMT status was available for 11/23 patients (7 unmethylated; 3 methylated; 1 inconclusive). Median tumor volume was 24.0 cm3 (SD = 31.1, 1.7-48.3 cm3). Median PFS was 11.5 months (95% CI 7.7-25.9) with 6, 12, 24 and 60 month PFS estimated to be 91.3% (95% CI 69.5-97.8), 47.4% (26.3-65.9), 32.5% (14.4-52.2) and 5.4% (0.4-21.8), respectively. Median OS was 23.1 months (95% CI 12.2-36.9) with 12, 24, and 36 month OS as 77.3% (95% CI 53.6-89.9), 45.0% (22.3-65.3) and 32.1% (12.5-53.8), respectively. CONCLUSIONS: Repeated dosing of IA BV after BBBD offers an encouraging outcome in terms of PFS and OS. Phase III trials are warranted to determine whether repeated IA BV combined with Stupp protocol is superior to Stupp protocol alone for newly diagnosed GBM.


Asunto(s)
Bevacizumab , Barrera Hematoencefálica , Neoplasias Encefálicas , Glioblastoma , Adulto , Anciano , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Barrera Hematoencefálica/patología , Neoplasias Encefálicas/tratamiento farmacológico , Esquema de Medicación , Glioblastoma/tratamiento farmacológico , Humanos , Infusiones Intraarteriales , Persona de Mediana Edad , Resultado del Tratamiento
5.
Eur J Neurol ; 28(9): 2989-3000, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34189814

RESUMEN

BACKGROUND AND PURPOSE: Radiomics provides a framework for automated extraction of high-dimensional feature sets from medical images. We aimed to determine radiomics signature correlates of admission clinical severity and medium-term outcome from intracerebral hemorrhage (ICH) lesions on baseline head computed tomography (CT). METHODS: We used the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial dataset. Patients included in this analysis (n = 895) were randomly allocated to discovery (n = 448) and independent validation (n = 447) cohorts. We extracted 1130 radiomics features from hematoma lesions on baseline noncontrast head CT scans and generated radiomics signatures associated with admission Glasgow Coma Scale (GCS), admission National Institutes of Health Stroke Scale (NIHSS), and 3-month modified Rankin Scale (mRS) scores. Spearman's correlation between radiomics signatures and corresponding target variables was compared with hematoma volume. RESULTS: In the discovery cohort, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.47 vs. 0.44, p = 0.008), admission NIHSS (0.69 vs. 0.57, p < 0.001), and 3-month mRS scores (0.44 vs. 0.32, p < 0.001). Similarly, in independent validation, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.43 vs. 0.41, p = 0.02), NIHSS (0.64 vs. 0.56, p < 0.001), and 3-month mRS scores (0.43 vs. 0.33, p < 0.001). In multiple regression analysis adjusted for known predictors of ICH outcome, the radiomics signature was an independent predictor of 3-month mRS in both cohorts. CONCLUSIONS: Limited by the enrollment criteria of the ATACH-2 trial, we showed that radiomics features quantifying hematoma texture, density, and shape on baseline CT can provide imaging correlates for clinical presentation and 3-month outcome. These findings couldtrigger a paradigm shift where imaging biomarkers may improve current modelsfor prognostication, risk-stratification, and treatment triage of ICH patients.


Asunto(s)
Hemorragia Cerebral , Hematoma , Hemorragia Cerebral/diagnóstico por imagen , Escala de Coma de Glasgow , Hematoma/diagnóstico por imagen , Humanos , Pronóstico , Tomografía Computarizada por Rayos X
6.
AJR Am J Roentgenol ; 217(4): 959-974, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33236647

RESUMEN

Neurologic involvement is well-recognized in COVID-19. This article reviews the neuroimaging manifestations of COVID-19 on CT and MRI, presenting cases from the New York City metropolitan region encountered by the authors during the first surge of the pandemic. The most common neuroimaging manifestations are acute infarcts with large clot burden and intracranial hemorrhage, including microhemorrhages. However, a wide range of additional imaging patterns occur, including leukoencephalopathy, global hypoxic injury, acute disseminated encephalomyelitis, cytotoxic lesions of the corpus callosum, olfactory bulb involvement, cranial nerve enhancement, and Guillain-Barré syndrome. The described CNS abnormalities largely represent secondary involvement from immune activation that leads to a prothrombotic state and cytokine storm; evidence for direct neuroinvasion is scant. Comorbidities such as hypertension, complications of prolonged illness and hospitalization, and associated supportive treatments also contribute to the CNS involvement in COVID-19. Routine long-term neurologic follow-up may be warranted, given emerging evidence of long-term microstructural and functional changes on brain imaging after COVID-19 recovery.


Asunto(s)
Encefalopatías/complicaciones , Encefalopatías/diagnóstico por imagen , COVID-19/complicaciones , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Encéfalo/diagnóstico por imagen , Humanos , Pandemias , SARS-CoV-2
7.
Stroke ; 51(9): e227-e231, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32757751

RESUMEN

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) evolved quickly into a global pandemic with myriad systemic complications, including stroke. We report the largest case series to date of cerebrovascular complications of COVID-19 and compare with stroke patients without infection. METHODS: Retrospective case series of COVID-19 patients with imaging-confirmed stroke, treated at 11 hospitals in New York, between March 14 and April 26, 2020. Demographic, clinical, laboratory, imaging, and outcome data were collected, and cases were compared with date-matched controls without COVID-19 from 1 year prior. RESULTS: Eighty-six COVID-19-positive stroke cases were identified (mean age, 67.4 years; 44.2% women). Ischemic stroke (83.7%) and nonfocal neurological presentations (67.4%) predominated, commonly involving multivascular distributions (45.8%) with associated hemorrhage (20.8%). Compared with controls (n=499), COVID-19 was associated with in-hospital stroke onset (47.7% versus 5.0%; P<0.001), mortality (29.1% versus 9.0%; P<0.001), and Black/multiracial race (58.1% versus 36.9%; P=0.001). COVID-19 was the strongest independent risk factor for in-hospital stroke (odds ratio, 20.9 [95% CI, 10.4-42.2]; P<0.001), whereas COVID-19, older age, and intracranial hemorrhage independently predicted mortality. CONCLUSIONS: COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical.


Asunto(s)
Trastornos Cerebrovasculares/etiología , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/etiología , Isquemia Encefálica/terapia , COVID-19 , Angiografía Cerebral , Trastornos Cerebrovasculares/mortalidad , Trastornos Cerebrovasculares/terapia , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/terapia , Etnicidad , Femenino , Mortalidad Hospitalaria , Humanos , Hemorragias Intracraneales/complicaciones , Hemorragias Intracraneales/mortalidad , Masculino , Persona de Mediana Edad , Neuroimagen , New York/epidemiología , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/terapia , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapia , Resultado del Tratamiento
8.
AJR Am J Roentgenol ; 214(1): 45-49, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31670589

RESUMEN

OBJECTIVE. This article provides comments from a small group of highly qualified reviewers of the American Journal of Roentgenology (AJR) regarding their approach to assessing manuscripts. The objective is to educate authors about the issues to which reviewers particularly attend and about errors that will decrease the likelihood of publication. CONCLUSION. By following the advice provided in this article, authors should be able to compose better manuscripts and reviewers should be able to generate better reviews.


Asunto(s)
Neurología , Revisión de la Investigación por Pares/normas , Publicaciones Periódicas como Asunto/normas , Edición/normas , Radiología , Guías como Asunto , Estados Unidos
9.
J Digit Imaging ; 32(5): 808-815, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30511281

RESUMEN

Aneurysm size correlates with rupture risk and is important for treatment planning. User annotation of aneurysm size is slow and tedious, particularly for large data sets. Geometric shortcuts to compute size have been shown to be inaccurate, particularly for nonstandard aneurysm geometries. To develop and train a convolutional neural network (CNN) to detect and measure cerebral aneurysms from magnetic resonance angiography (MRA) automatically and without geometric shortcuts. In step 1, a CNN based on the U-net architecture was trained on 250 MRA maximum intensity projection (MIP) images, then applied to a testing set. In step 2, the trained CNN was applied to a separate set of 14 basilar tip aneurysms for size prediction. Step 1-the CNN successfully identified aneurysms in 85/86 (98.8% of) testing set cases, with a receiver operating characteristic (ROC) area-under-the-curve of 0.87. Step 2-automated basilar tip aneurysm linear size differed from radiologist-traced aneurysm size on average by 2.01 mm, or 30%. The CNN aneurysm area differed from radiologist-derived area on average by 8.1 mm2 or 27%. CNN correctly predicted the area trend for the set of aneurysms. This approach is to our knowledge the first using CNNs to derive aneurysm size. In particular, we demonstrate the clinically pertinent application of computing maximal aneurysm one-dimensional size and two-dimensional area. We propose that future work can apply this to facilitate pre-treatment planning and possibly identify previously missed aneurysms in retrospective assessment.


Asunto(s)
Angiografía Cerebral/métodos , Interpretación de Imagen Asistida por Computador/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Angiografía por Resonancia Magnética/métodos , Redes Neurales de la Computación , Humanos , Estudios Retrospectivos
10.
J Exp Ther Oncol ; 12(3): 223-229, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29790314

RESUMEN

OBJECTIVE: We describe the first case of a novel treatment for a newly diagnosed glioblastoma (GBM) using superselective intraarterial cerebral infusion (SIACI) of cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol. A 51year-old female underwent craniotomy for removal of a right frontal GBM. Pathology confirmed EGFR amplification, and she underwent three treatments of SIACI of cetuximab to the tumor site. The first treatment was given within a week of starting standard of care chemoradiation (Stupp protocol), which is a combination of radiation treatment (2 Gy per/ day x 30 days, total of 60 Gy) and oral temozolomide (75 mg/m2). The second and third SIACI of cetuximab were administered 3 and 6 months later, while the patient continued on maintenance temozolomide. Post-radiation changes on MRI were stable, and there were no signs of recurrence at 4 and 6 months post-resection. Herein, we detail the technical aspects of this novel treatment paradigm and suggest that SIACI of cetuximab after BBB disruption using mannitol, combined with the standard of care chemoradiation therapy, may be an effective treatment method for newly diagnosed EGFR amplified glioblastoma.


Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Barrera Hematoencefálica/efectos de los fármacos , Neoplasias Encefálicas/terapia , Cetuximab/administración & dosificación , Dacarbazina/análogos & derivados , Fraccionamiento de la Dosis de Radiación , Glioblastoma/terapia , Manitol/uso terapéutico , Angiografía de Substracción Digital , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Angiografía Cerebral/métodos , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Craneotomía , Dacarbazina/administración & dosificación , Femenino , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Infusiones Intraarteriales , Imagen por Resonancia Magnética , Persona de Mediana Edad , Temozolomida , Resultado del Tratamiento
11.
AJR Am J Roentgenol ; 210(1): 30-38, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28981352

RESUMEN

OBJECTIVE: The purpose of this review is to summarize advances in the molecular analysis of gliomas, the role genetics plays in MRI features, and how machine-learning approaches can be used to survey the tumoral environment. CONCLUSION: The genetic profile of gliomas influences the course of treatment and clinical outcomes. Though biopsy is the reference standard for determining tumor genetics, it can suffer diagnostic delays due to surgical planning and pathologic assessment. Radiogenomics may allow rapid, low-risk characterization of genetic heterogeneity.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Heterogeneidad Genética , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Humanos , Imagen por Resonancia Magnética
12.
J Exp Ther Oncol ; 12(1): 67-71, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28472567

RESUMEN

OBJECTIVE: Standard treatment for recurrent GBM is not yet established. We present a case demonstrating the benefit of intra-arterial (IA) bevacizumab with blood brain barrier disruption (BBBD) for the treatment of recurrent GBM. A 31 year-old man diagnosed with GBM, following primary resection, received temozolomide. After a second resection, he received one dose of IA bevacizumab with BBBD using mannitol, preventing regrowth for 2.5 years. Following tumor regrowth, the patient received another dose of IA bevacizumab with BBBD, which has prevented regrowth for another year.


Asunto(s)
Bevacizumab/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Barrera Hematoencefálica/efectos de los fármacos , Dacarbazina/análogos & derivados , Dacarbazina/uso terapéutico , Humanos , Masculino , Temozolomida
14.
AJR Am J Roentgenol ; 208(1): 57-65, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27726412

RESUMEN

OBJECTIVE: Recurrence of glioblastoma multiforme (GBM) arises from areas of microscopic tumor infiltration that have yet to disrupt the blood-brain barrier. We hypothesize that these microscopic foci of invasion cause subtle variations in the apparent diffusion coefficient (ADC) and FLAIR signal detectable with the use of computational big-data modeling. MATERIALS AND METHODS: Twenty-six patients with native GBM were studied immediately after undergoing gross total tumor resection. Within the peritumoral region, areas of future GBM recurrence were identified through coregistration of follow-up MRI examinations. The likelihood of tumor recurrence at each individual voxel was assessed as a function of signal intensity on ADC maps and FLAIR images. Both single and combined multivariable logistic regression models were created. RESULTS: A total of 419,473 voxels of data (105,477 voxels of data within tumor recurrence and 313,996 voxels of data on surrounding peritumoral edema) were analyzed. For future areas of recurrence, a 9.5% decrease in the ADC value (p < 0.001) and a 9.2% decrease in signal intensity on FLAIR images (p < 0.001) were shown, compared with findings for the surrounding peritumoral edema. Logistic regression revealed that the amount of signal loss on both ADC maps and FLAIR images correlated with the likelihood of tumor recurrence. A combined multiparametric logistic regression model was more specific in the prediction of tumor recurrence than was either single-variable model alone. CONCLUSION: Areas of future GBM recurrence exhibit small but highly statistically significant differences in signal intensity on ADC maps and FLAIR images months before the development of abnormal enhancement occurs. A multiparametric logistic model calibrated to these changes can be used to estimate the burden of microscopic nonenhancing tumor and predict the location of recurrent disease. Computational big-data modeling performed at the voxel level is a powerful technique capable of discovering important but subtle patterns in imaging data.


Asunto(s)
Algoritmos , Neoplasias Encefálicas/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Glioblastoma/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Carga Tumoral
15.
J Exp Ther Oncol ; 11(4): 261-267, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27849336

RESUMEN

BACKGROUND: Bevacizumab (BV) has been used to treat recurrent glioblastoma with a progression free survival of approximately 3-3.5 months. Typically, it is administered intravenously every 2-3 weeks at dosages ranging from 5-15 mg/kg. Serious side effects include GI tract perforations, hematologic disorders, intracranial hemorrhage, and malignant hypertension. We hypothesized that selective intracranial intra-arterial infusion (SIACI) of BV following blood/brain barrier disruption (BBBD) with mannitol may allow for reduced dosage, lower toxicity, and equivalent or superior progression free survival (PFS). METHODS: Sixteen patients (8 males & 8 females) with a mean age of 55 years (range 27-68), KPS>70, and recurrent glioblastoma were enrolled. All patients underwent super-selective catheterization and were given a single intra-arterial dose of 15 mg/kg BV following osmotic blood/brain barrier disruption with mannitol to the arteries supplying the tumor. The patients had no additional treatment following that initial SIACI mannitol and BV until they met criteria for progression. PFS was assessed using modified Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: Median progression free survival from only one dose of SIACI mannitol and BV was 3.9 months. Side effects included seizure in 2 patients, and headache in 1 patient. Seizures were well controlled with medications, and there were no serious toxicities. There were no endovascular-related complications. CONCLUSION: SIACI of mannitol and BV at 15mg/kg allows for similar or better PFS compared to biweekly treatments of IV BV at 10mg/kg. The dosage required is lower and side effects were minimal and well tolerated. Future larger trials are warranted to assess whether repeated less frequent IA mannitol and BV may be superior to biweekly IV administration as a monotherapy.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Bevacizumab/administración & dosificación , Barrera Hematoencefálica/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intraarteriales/métodos , Masculino , Manitol/uso terapéutico , Persona de Mediana Edad
16.
J Exp Ther Oncol ; 11(4): 293-301, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27849340

RESUMEN

IMPORTANCE: Management of recurrent head and neck squamous cell carcinoma is a common and challenging clinical problem in head and neck oncology. OBJECTIVE: Here we present the first reported case of super-selective intra-arterial (SSIA) microcatheter based local delivery of cetuximab for head and neck cancer. This technical report describes the techniques used to deliver the SSIA dose of cetuximab, as well as the patient outcome. DESIGN: This technical report is part of an ongoing Phase I Clinical Trial. SETTING: The New York Head and Neck Institute (NYHNI) is a full-service otolaryngology and neurosurgery department at Lenox Hill Hospital, part of the Northwell Health System. The NYHNI serves a diverse patient population with a wide range of head and neck diseases in a tertiary hospital setting. INTERVENTION: SSIA Cetuximab. PARTICIPANT: A patient presents to our clinic with recurrent unresectable squamous cell carcinoma of the nasopharynx. He is recruited into the first cohort of a phase I clinical trial to assess the safety of SSIA cetuximab, dose starting at 100mg/m2. Adjuvant chemo-radiation therapy is also given. MEASURES: Safety, as measured by toxicity of SSIA cetuximab. RESULTS: SSIA Cetuximab has been demonstrated to be a safe and feasible procedure in this technical report. CONCLUSIONS: This case illustrates technical feasibility and a very preliminary assessment of the safety of a novel delivery of a biologic agent for squamous cell carcinoma of the head and neck, which is part of an ongoing phase I clinical trial. TRIAL REGISTRATION: NCT02438995.


Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Cetuximab/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Humanos , Masculino
17.
J Neurooncol ; 128(3): 405-15, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26945581

RESUMEN

Objective To establish a maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of Cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol, and examine safety of the procedure in patients with recurrent malignant glioma. Methods A total of 15 patients with recurrent malignant glioma were included in the current study. The starting dose of Cetuximab was 100 mg/m(2) and dose escalation was done to 250 mg/m(2). All patients were observed for 28 days post-infusion for any side effects. Results There was no dose-limiting toxicity from a single dose of SIACI of Cetuximab up to 250 mg/m(2) after osmotic BBB disruption with mannitol. A tolerable rash was seen in 2 patients, anaphylaxis in 1 patient, isolated seizure in 1 patient, and seizure and cerebral edema in 1 patient. Discussion SIACI of mannitol followed by Cetuximab (up to 250 mg/m(2)) for recurrent malignant glioma is safe and well tolerated. A Phase I/II trial is currently underway to determine the efficacy of SIACI of cetuximab in patients with high-grade glioma.


Asunto(s)
Antineoplásicos Inmunológicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Cetuximab/administración & dosificación , Diuréticos Osmóticos/uso terapéutico , Glioma/tratamiento farmacológico , Manitol/uso terapéutico , Adulto , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Cetuximab/efectos adversos , Quimioterapia Combinada , Femenino , Glioma/diagnóstico por imagen , Glioma/metabolismo , Humanos , Infusiones Intraarteriales , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/metabolismo , Resultado del Tratamiento
18.
AJR Am J Roentgenol ; 206(5): 1073-81, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27007449

RESUMEN

OBJECTIVE: Glioblastoma is an invasive primary brain malignancy that typically infiltrates the surrounding tissue with malignant cells. It disrupts cerebral blood flow through a variety of biomechanical and biochemical mechanisms. Thus, neuroimaging focused on identifying regions of vascular dysregulation may reveal a marker of tumor spread. The purpose of this study was to use blood oxygenation level-dependent (BOLD) functional MRI (fMRI) to compare the temporal dynamics of the enhancing portion of a tumor with those of brain regions without apparent tumors. MATERIALS AND METHODS: Patients with pathologically proven glioblastoma underwent preoperative resting-state BOLD fMRI, T1-weighted contrast-enhanced MRI, and FLAIR MRI. The contralesional control hemisphere, contrast-enhancing tumor, and peritu-moral edema were segmented by use of structural images and were used to extract the time series of these respective regions. The parameter estimates (beta values) for the two regressors and resulting z-statistic images were used as a metric to compare the similarity of the tumor dynamics to those of other brain regions. RESULTS: The time course of the contrast-enhancing tumor was significantly different from that of the rest of the brain (p < 0.05). Similarly, the control signal intensity was significantly different from the tumor signal intensity (p < 0.05). Notably, the temporal dynamics in the peritumoral edema, which did not contain enhancing tumor, were most similar to the those of enhancing tumor than to those of control regions. CONCLUSION: The findings show that the disruption in vascular regulation induced by a glioblastoma can be detected with BOLD fMRI and that the spatial distribution of these disruptions is localized to the immediate vicinity of the tumor and peritumoral edema.


Asunto(s)
Neoplasias Encefálicas/fisiopatología , Trastornos Cerebrovasculares/fisiopatología , Glioblastoma/fisiopatología , Adulto , Anciano , Encéfalo , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/diagnóstico , Circulación Cerebrovascular/fisiología , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/diagnóstico , Medios de Contraste , Edema/sangre , Edema/fisiopatología , Femenino , Glioblastoma/sangre , Glioblastoma/diagnóstico , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxígeno/sangre
19.
J Magn Reson Imaging ; 42(6): 1623-30, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26032694

RESUMEN

BACKGROUND: To apply quantitative whole-brain T1 -rho (T1ρ ) and T2 imaging to the detection and quantification of brain changes resulting from multiple sclerosis (MS). METHODS: Twenty-three MS patients with clinically isolated syndrome (10) and relapsing remitting MS (13) phenotypes, compared with 24 age-matched healthy controls were imaged at 3 Tesla. An axial T1ρ -weighted three-dimensional turbo spin echo sequence with a variable flip angle and fluid suppression was used. Spin-lock times of 0, 20, 40, 60, 80, and 100 ms were used. Corresponding T2 maps were also acquired. RESULTS: Whole brain white matter (WM) T1ρ maps were elevated compared with controls (P = 0.002). WM lesion T1ρ and T2 values were highly correlated (r = 0.83), but T1ρ demonstrated 25% better contrast to noise ratio (P < 0.001). WM lesion T1ρ correlated with disease duration. Gray matter T1ρ was negatively correlated with the Expanded Disability Status Scale, r = -0.45, P = 0.03. Normal appearing gray matter and cortical gray matter lesions were negatively correlated on T1ρ , but not on T2 (rT1ρ = -0.63, pT1ρ = 0.03; rT2 = -0.17, pT2 = 0.6). CONCLUSION: T1ρ MRI demonstrates enhanced lesion contrast compared with T2 , and in some cases may provide complementary information. T1ρ may provide a useful measure of demyelinating processes in MS.


Asunto(s)
Algoritmos , Encéfalo/patología , Sustancia Gris/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/patología , Adulto , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
20.
AJR Am J Roentgenol ; 204(1): W52-7, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25539275

RESUMEN

UNLABELLED: OBJECTIVE; There is evidence in academic medicine that the number of authors per paper has increased over time. The goal of this study was to quantitatively analyze authorship trends in the field of radiology over 20 years. MATERIALS AND METHODS: A search of the National Library of Medicine MEDLINE database was conducted to identify articles published by radiology departments between 1991 and 2012. Country of origin, article study design, and journal impact factor were recorded. The increase in number of authors per paper was assessed by linear and nonlinear regression. Pearson correlation was used to assess the relation between journal impact factor and number of authors. RESULTS: A total of 142,576 articles and 699,257 authors were identified during the study period. The mean number of authors per paper displayed linear growth from 3.9 to 5.7 (p < 0.0001). The proportion of single authors declined from 11% in 1991 to 4.4% in 2012. The number of clinical trials increased in a linear pattern, review articles in an exponential pattern, and case reports in a logistic pattern (p < 0.0001 for each). Countries with the highest number of authors per paper were Japan, Italy, and Germany. The number of articles funded by the U.S. National Institutes of Health (NIH) displayed exponential growth and of non-NIH-funded articles displayed linear growth (p < 0.0001 for each). A negligible relation was observed between journal impact factor and number of authors (Pearson r = 0.1066). CONCLUSION: Radiology has had a steady increase in mean number of authors per paper since the early 1990s that has varied by study design. The increase is probably multi-factorial and includes components of author inflation and increasing complexity of research. Findings support the need for reemphasis of authorship criteria to preserve authorship value and accountability.


Asunto(s)
Autoria , Bibliometría , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Publicaciones Periódicas como Asunto/tendencias , Edición/estadística & datos numéricos , Edición/tendencias , Radiología/estadística & datos numéricos , Internacionalidad
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