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Currently, computed tomography and conventional X-ray radiography usually generate a micro-artifact around metal implants. This metal artifact frequently causes false positive or negative diagnoses of bone maturation or pathological peri-implantitis around implants. In an attempt to repair the artifacts, a highly specific nanoprobe, an osteogenic biomarker, and nano-Au-Pamidronate were designed to monitor the osteogenesis. In total, 12 Sprague Dawley rats were included in the study and could be chategorized in 3 groups: 4 rats in the X-ray and CT group, 4 rats in the NIRF group, and 4 rats in the sham group. A titanium alloy screw was implanted in the anterior hard palate. The X-ray, CT, and NIRF images were taken 28 days after implantation. The X-ray showed that the tissue surrounded the implant tightly; however, a gap of metal artifacts was noted around the interface between dental implants and palatal bone. Compared to the CT image, a fluorescence image was noted around the implant site in the NIRF group. Furthermore, the histological implant-bone tissue also exhibited a significant NIRF signal. In conclusion, this novel NIRF molecular imaging system precisely identifies the image loss caused by metal artifacts and can be applied to monitoring bone maturation around orthopedic implants. In addition, by observing the new bone formation, a new principle and timetable for an implant osseointegrated with bone can be established and a new type of implant fixture or surface treatment can be evaluated using this system.
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Implantes Dentales , Oseointegración , Ratas , Animales , Osteogénesis , Ratas Sprague-Dawley , Maxilar , Prótesis e Implantes , TitanioRESUMEN
PURPOSE: Gamma-aminobutyric acid (GABA) abnormalities have been implicated in a range of neuropsychiatric disorders. Despite substantial interest in probing GABA in vivo, human imaging studies relying on magnetic resonance spectroscopy (MRS) have generally been hindered by technical challenges, including GABA's relatively low concentration and spectral overlap with other metabolites. Although past studies have shown moderate-to-strong test-retest repeatability and reliability of GABA within certain brain regions, many of these studies have been limited by small sample sizes. METHODS: GABA+ (macromolecular-contaminated) test-retest reliability and repeatability were assessed via a Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) MRS sequence in the rostral anterior cingulate cortex (rACC; n = 21) and dorsolateral prefrontal cortex (dlPFC; n = 20) in healthy young adults. Data were collected on a 3T scanner (Siemens Prisma, Siemens Healthcare, Erlangen, Germany) and GABA+ results were reported in reference to both total creatine (GABA+/tCr) and water (GABA+/water). RESULTS: Results showed strong test-retest repeatability (mean GABA+/tCr coefficient of variation [CV] = 4.6%; mean GABA+/water CV = 4.0%) and reliability (GABA+/tCr intraclass correlation coefficient [ICC] = 0.77; GABA+/water ICC = 0.87) in the dlPFC. The rACC showed acceptable (but comparatively lower) repeatability (mean GABA+/tCr CV = 8.0%; mean GABA+/water CV = 7.5%), yet low-moderate reliability (GABA+/tCr ICC = 0.40; GABA+/water ICC = 0.44). CONCLUSION: The present study found excellent GABA+ MRS repeatability and reliability in the dlPFC. The rACC showed inferior results, possibly because of a combination of shimming impedance and measurement error. These data suggest that MEGA-PRESS can be utilized to reliably distinguish participants based on dlPFC GABA+ levels, whereas the mixed results in the rACC merit further investigation.
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Imagen por Resonancia Magnética , Ácido gamma-Aminobutírico , Alemania , Humanos , Espectroscopía de Resonancia Magnética , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
OBJECTIVE: Preclinical work suggests that excess glucocorticoids and reduced cortical γ-aminobutyric acid (GABA) may affect sex-dependent differences in brain regions implicated in stress regulation and depressive phenotypes. The authors sought to address a critical gap in knowledge, namely, how stress circuitry is functionally affected by glucocorticoids and GABA in current or remitted major depressive disorder (MDD). METHODS: Multimodal imaging data were collected from 130 young adults (ages 18-25), of whom 44 had current MDD, 42 had remitted MDD, and 44 were healthy comparison subjects. GABA+ (γ-aminobutyric acid and macromolecules) was assessed using magnetic resonance spectroscopy, and task-related functional MRI data were collected under acute stress and analyzed using data-driven network modeling. RESULTS: Across modalities, trait-related abnormalities emerged. Relative to healthy comparison subjects, both clinical groups were characterized by lower rostral anterior cingulate cortex (rACC) GABA+ and frontoparietal network amplitude but higher amplitude in salience and stress-related networks. For the remitted MDD group, differences from the healthy comparison group emerged in the context of elevated cortisol levels, whereas the MDD group had lower cortisol levels than the healthy comparison group. In the comparison group, frontoparietal and stress-related network connectivity was positively associated with cortisol level (highlighting putative top-down regulation of stress), but the opposite relationship emerged in the MDD and remitted MDD groups. Finally, rACC GABA+ was associated with stress-induced changes in connectivity between overlapping default mode and salience networks. CONCLUSIONS: Lifetime MDD was characterized by reduced rACC GABA+ as well as dysregulated cortisol-related interactions between top-down control (frontoparietal) and threat (task-related) networks. These findings warrant further investigation of the role of GABA in the vulnerability to and treatment of MDD.
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Trastorno Depresivo Mayor , Giro del Cíngulo , Hidrocortisona , Imagen por Resonancia Magnética , Imagen Multimodal , Estrés Psicológico , Ácido gamma-Aminobutírico , Humanos , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Masculino , Hidrocortisona/metabolismo , Femenino , Adulto , Adulto Joven , Ácido gamma-Aminobutírico/metabolismo , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Adolescente , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Estrés Psicológico/diagnóstico por imagen , Espectroscopía de Resonancia Magnética , Conectoma , Estudios de Casos y Controles , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagenRESUMEN
BACKGROUND: Neurocognitive factors including aberrant reward learning, blunted GABA (gamma-aminobutyric acid), and potentiated stress sensitivity have been linked to anhedonia, a hallmark depressive symptom, possibly in a sex-dependent manner. However, previous research has not investigated the putative associations among these factors or the extent to which they represent trait- or state-based vulnerabilities for depression. METHODS: Young adults with current major depressive disorder (MDD) (n = 44), remitted MDD (n = 42), and healthy control participants (HCs) (n = 44), stratified by sex assigned at birth, underwent magnetic resonance spectroscopy to assess macromolecular contaminated GABA (GABA+) and then a reward learning task before and after acute stress. We assessed changes in reward learning after stress and associations with GABA+. RESULTS: Results revealed blunted baseline reward learning in participants with remitted MDD versus participants with current MDD and HCs but, surprisingly, no differences between participants with current MDD and HCs. Reward learning was reduced following acute stress regardless of depressive history. GABA+ in the rostral anterior cingulate cortex, but not the dorsolateral prefrontal cortex, was associated with reduced baseline reward learning only in female participants. GABA+ did not predict stress-related changes in reward learning. CONCLUSIONS: To our knowledge, this is the first study to investigate associations among GABA, reward learning, and stress reactivity in current versus past depression. Hypothesized depression-related differences in reward learning did not emerge, precluding claims about state versus trait vulnerabilities. However, our finding that blunted GABA was associated with greater reward learning in female participants provides novel insights into sex-selective associations between the frontal GABAergic inhibitory system and reward processing.
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Trastorno Depresivo Mayor , Recompensa , Estrés Psicológico , Ácido gamma-Aminobutírico , Humanos , Femenino , Masculino , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/metabolismo , Adulto Joven , Ácido gamma-Aminobutírico/metabolismo , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Adulto , Aprendizaje/fisiología , Giro del Cíngulo/metabolismo , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/diagnóstico por imagen , Espectroscopía de Resonancia Magnética , Caracteres Sexuales , Factores Sexuales , AdolescenteRESUMEN
Voriconazole is more effective for aspergillosis infections with central nervous system involvement than other antifungal agents. The clinical efficacy of voriconazole for central nervous system infections has been attributed to its ability to cross the blood-brain barrier. However, pharmacokinetic studies are limited to plasma and cerebrospinal fluid, so it remains unclear how much of the drug enters the brain. Fluorinated compounds such as voriconazole can be quantified in the brain using fluorine-19 magnetic resonance spectroscopy (MRS). Twelve healthy adult males participated in a pharmacokinetic analysis of voriconazole levels in the brain and plasma. Open-label voriconazole was dosed per clinical protocol with a loading dose of 400 mg every 12 h on day 1, followed by 200 mg every 12 h administered orally over a 3-day period. MRS was performed before and after dosing on the third day. Voriconazole levels in the brain exceeded the MIC for Aspergillus. The brain/plasma ratios were 3.0 at steady state on day 3 (predose) and 1.9 postdose. We found that voriconazole is able to penetrate the brain tissue, which can be quantified using a noninvasive MRS technique. (This study has been registered at ClinicalTrials.gov under registration no. NCT00300677.).
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Antifúngicos/farmacocinética , Encéfalo/metabolismo , Pirimidinas/farmacocinética , Triazoles/farmacocinética , Administración Oral , Adulto , Antifúngicos/sangre , Área Bajo la Curva , Barrera Hematoencefálica/metabolismo , Esquema de Medicación , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Pirimidinas/sangre , Triazoles/sangre , VoriconazolRESUMEN
OBJECTIVE: To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications. METHODS: We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed. RESULTS: The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-α (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-α were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time. CONCLUSIONS: Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups.
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Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/etiología , Neuropatías Diabéticas/etiología , Ejercicio Físico , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Fosforilación Oxidativa , Enfermedad Arterial Periférica/etiología , Fosfocreatina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/fisiopatología , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/fisiopatología , Femenino , Factor Estimulante de Colonias de Granulocitos/sangre , Humanos , Mediadores de Inflamación/sangre , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Contracción Muscular , Músculo Esquelético/fisiopatología , Osteoprotegerina/sangre , Enfermedad Arterial Periférica/metabolismo , Enfermedad Arterial Periférica/fisiopatología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Prefrontal and striatal glutamate plays an important role in modulating striatal dopamine levels and an imbalance in regional glutamate has been identified in several psychiatric conditions. We hypothesized that this imbalance also exists in cannabis use disorder (CUD). We recently quantified the difference in glutamate of dorsal anterior cingulate (dACC) and striatum regions in the frontostriatal pathway using proton MRS at baseline and on verified abstinent days 7 and 21 in chronic users of cannabis (n = 20) in comparison with age- and sex- matched non-using controls (n = 10). In addition, the Barratt Impulsiveness Scale-11 (BIS) was collected as a measure of inhibitory impulse control of the participants. We found that the difference in glutamate concentrations between the dACC and striatum (ΔdACC-strGlu) of the controls was significantly higher than that of cannabis users across the study timeline (F(1,28) = 18.32, p < 0.0005). The group difference was not affected by age, sex, or alcohol/cigarette consumption. On abstinent day 7, ΔdACC-strGlu was significantly correlated with the corresponding ΔdACC-strGABA among the users (r = 0.837, p < 0.00001). On day 21, ΔdACC-strGlu was negatively associated with monthly cannabis use days (Spearman's rho = -0.444, p = 0.05). Self-reported BIS and its subscales were significantly altered among the users compared to the controls across the study timeline (total F(1,28) = 7.0, p = 0.013; non-planning F(1,28) = 16.1, p < 0.0005; motor F(1,28) = 5.9, p = 0.022; cognitive F(1,28) = 6.1, p = 0.019). These data provide preliminary evidence that chronic cannabis use may lead to a dACC-striatal glutamate imbalance in conjunction with poor impulse control.
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Cannabis , Alucinógenos , Humanos , Giro del Cíngulo/metabolismo , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Agonistas de Receptores de Cannabinoides , Ácido Glutámico/metabolismo , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: Despite the prevalence, associated comorbidities, and functional consequences of bipolar depression (BPD), underlying disease mechanisms remain unclear. Published studies of individuals with bipolar disorder implicate abnormalities in cellular energy metabolism. This study tests the hypotheses that the forward rate constant (k(for)) of creatine kinase (CK) is altered in older adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that enhance mitochondrial function, increases k(for) in elderly individuals with BPD treated with CoQ10 compared with untreated age- and sex-matched controls. METHODS: Ten older adults (ages 55 and above) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current episode depressed and 8 older controls underwent two 4 Tesla (31)Phosphorus magnetic resonance spectroscopy ((31)PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate k(for). The BPD group was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2 weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale (MADRS) was used to measure depression symptom severity. Baseline k(for) and changes in k(for) were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with k(for) changes using repeated measures linear regression. RESULTS: The k(for) of CK was nonsignificantly lower for BPD than healthy controls at baseline (BPD mean (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02), Wilcoxon rank sum exact P = .40). The k(for) for both CoQ10-treated BPD and controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon signed rank exact P = .01), with no significant difference in 8-week changes between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) = 0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory analysis, depression severity decreased with CoQ10 treatment in the group with BPD (F (3,7) = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t (9) = -2.40, P = .04) and 4 (t (9) = -3.80, P = .004). CONCLUSIONS: This study employing the novel MRS technique of MT did not demonstrate significance between group differences in the k(for) of CK but did observe a trend that would require confirmation in a larger study. An exploratory analysis suggested a reduction in depression symptom severity during treatment with high-dose CoEnzyme Q10 for older adults with BPD. Further studies exploring alterations of high-energy phosphate metabolites in geriatric BPD and efficacy studies of CoQ10 in a randomized controlled trial are both warranted.
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Afecto/efectos de los fármacos , Trastorno Bipolar/enzimología , Creatina Quinasa/metabolismo , Ubiquinona/análogos & derivados , Afecto/fisiología , Anciano , Trastorno Bipolar/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Estudios de Casos y Controles , Creatina Quinasa/efectos de los fármacos , Creatina Quinasa/fisiología , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Estadísticas no Paramétricas , Ubiquinona/metabolismo , Ubiquinona/fisiología , Ubiquinona/uso terapéuticoRESUMEN
Glutamate plays an important role in continued use of and relapse to abused substances. However, its involvement in cannabis withdrawal is still unclear. We hypothesize that regional glutamate is associated with the cannabis withdrawal syndrome and recently examined possible association of glutamate with cannabis withdrawal, using magnetic resonance spectroscopy (MRS), in non-treatment-seeking cannabis users. We recruited 26 frequent cannabis users and 11 age-matched non-using controls. Of the 37, 20 users (8f/12m) and 10 controls (5f/5m) completed a verified 21-day abstinence protocol. Dorsal anterior cingulate cortex (dACC) glutamate and γ-amino butyric acid (GABA) were measured with proton MRS at baseline and on abstinent days 7 and 21 in conjunction with measures of cannabis withdrawal and craving (MCQ), sleep difficulties (PSQI) and mood state. We used ANOVA to examine group differences in glutamate and GABA from baseline through day 21 and used linear regression to evaluate correlations between intra-individual glutamate and withdrawal symptoms. We found that self-reported anxiety severity (HAMA) was correlated with urinary THC/Cr ratios at baseline (r = 0.768, p = 0.000076) and abstinent day 7 (r = 0.5636, p = 0.0097), dACC glutamate was significantly lower in the users compared with the controls from baseline through day 21 (F = 5.90, p = 0.022), changes in glutamate between baseline and abstinent day 21 had a significantly negative correlation with corresponding changes in craving (r = -0.72, p = 0.005) after adjusting for age, consumption of alcohol/cigarettes, sleep difficulties, and urinary THC levels. These findings provide preliminary evidence that dACC glutamate is associated with the cannabis withdrawal syndrome.
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Cannabis , Alucinógenos , Trastornos del Inicio y del Mantenimiento del Sueño , Síndrome de Abstinencia a Sustancias , Agonistas de Receptores de Cannabinoides , Dronabinol , Ácido Glutámico , Giro del Cíngulo/diagnóstico por imagen , Humanos , Protones , Ácido gamma-AminobutíricoRESUMEN
Cannabis withdrawal symptoms contribute to relapse, but the underlying mechanism remains unclear. We hypothesize that cannabis withdrawal may be associated with a reset of regional γ-amino butyric acid (GABA) and glutamate concentrations secondary to changes in the endocannabinoid system during abstinence and conducted a study on this issue. We used magnetic resonance spectroscopy (MRS) to detect the associated changes of these neurochemicals in twenty-six frequent, recreational cannabis users and eleven age-matched non-using controls. Twenty users (8F/12M) and ten control (5F/5M) participants completed a verified 21-day abstinence period. Striatal GABA and glutamine concentrations were measured at baseline and on abstinence days 7 and 21 in conjunction with measures of cannabis withdrawal symptoms and mood state. Cannabis users reported increased self-reported ratings of cannabis-withdrawal-symptoms on abstinence day 7 relative to controls. Striatal glutamate + glutamine (Glx) group concentrations were elevated in cannabis users at baseline and abstinence days 7 and 21 (F = 7.16, p = 0.012), and changes in GABA concentration and withdrawal symptoms between baseline and abstinence day 7 were positively correlated (r = 0.550, p = 0.010). In addition, baseline striatal GABA concentrations were negatively correlated with withdrawal symptoms on abstinence day 7 (r = -0.680, p = 0.003). Our data demonstrate that striatal Glx was elevated in cannabis users and baseline striatal GABA correlated with withdrawal during the abstinence. In addition, striatal GABA may temporally correlate with self-reported withdrawal symptoms during the initial days of abrupt cannabis abstinence. These findings provide preliminary evidence that striatal GABA and Glx are associated with the severity of cannabis withdrawal.
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Cannabis , Alucinógenos , Síndrome de Abstinencia a Sustancias , Cannabis/efectos adversos , Ácido Glutámico , Glutamina , Humanos , Ácido gamma-AminobutíricoRESUMEN
The interplay between cortical and limbic regions in stress circuitry calls for a neural systems approach to investigations of acute stress responses in major depressive disorder (MDD). Advances in multimodal imaging allow inferences between regional neurotransmitter function and activation in circuits linked to MDD, which could inform treatment development. The current study investigated the role of the inhibitory neurotransmitter GABA in stress circuitry in females with current and remitted MDD. Multimodal imaging data were analyzed from 49 young female adults across three groups (current MDD, remitted MDD (rMDD), and healthy controls). GABA was assessed at baseline using magnetic resonance spectroscopy, and functional MRI data were collected before, during, and after an acute stressor and analyzed using a network modeling approach. The MDD group showed an overall lower cortisol response than the rMDD group and lower rostral anterior cingulate cortex (ACC) GABA than healthy controls. Across groups, stress decreased activation in the frontoparietal network (FPN) but increased activation in the default mode network (DMN) and a network encompassing the ventromedial prefrontal cortex-striatum-anterior cingulate cortex (vmPFC-Str-ACC). Relative to controls, the MDD and rMDD groups were characterized by decreased FPN and salience network (SN) activation overall. Rostral ACC GABA was positively associated with connectivity between an overlapping limbic network (Temporal-Insula-Amygdala) and two other circuits (FPN and DMN). Collectively, these findings indicate that reduced GABA in females with MDD was associated with connectivity differences within and across key networks implicated in depression. GABAergic treatments for MDD might alleviate stress circuitry abnormalities in females.
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Trastorno Depresivo Mayor , Adulto , Mapeo Encefálico , Depresión , Trastorno Depresivo Mayor/diagnóstico por imagen , Femenino , Giro del Cíngulo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Imagen Multimodal , Ácido gamma-AminobutíricoRESUMEN
A molecular imaging probe comprising superparamagnetic iron oxide (SPIO) nanoparticles and Mycobacterium tuberculosis surface antibody (MtbsAb) was synthesized to enhance imaging sensitivity for extrapulmonary tuberculosis (ETB). An SPIO nanoprobe was synthesized and conjugated with MtbsAb. The purified SPIO-MtbsAb nanoprobe was characterized using TEM and NMR. To determine the targeting ability of the probe, SPIO-MtbsAb nanoprobes were incubated with Mtb for in vitro imaging assays and injected into Mtb-inoculated mice for in vivo investigation with magnetic resonance (MR). The contrast enhancement reduction on magnetic resonance imaging (MRI) of Mtb and THP1 cells showed proportional to the SPIO-MtbsAb nanoprobe concentration. After 30 min of intravenous SPIO-MtbsAb nanoprobe injection into Mtb-infected mice, the signal intensity of the granulomatous site was enhanced by 14-fold in the T2-weighted MR images compared with that in mice receiving PBS injection. The MtbsAb nanoprobes can be used as a novel modality for ETB detection.
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Dextranos/síntesis química , Nanopartículas de Magnetita/química , Tuberculosis/diagnóstico , Animales , Anticuerpos Antibacterianos/inmunología , Compuestos Férricos , Humanos , Inyecciones Intravenosas , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/ultraestructura , Ratones Endogámicos C57BL , Mycobacterium tuberculosis/inmunología , Tamaño de la Partícula , Células THP-1 , Tuberculosis/inmunología , Tuberculosis/microbiología , Tuberculosis/patologíaRESUMEN
A precise imaging technique to evaluate osteogenesis, osteodifferentiation, and osseointegration following peri-implant surgery is in high clinical demand. Herein, we report the generation of two new, near-infrared (NIR) fluorescent probes for use in the molecular imaging of bone repair. The first probe aims to monitor the in vitro differentiation of human mesenchymal stem cells (MSCs) into osteoblasts. A NIR fluorochrome was conjugated to a cyclic peptide that binds to integrin α5ß1, a factor that promotes osteogenesis in MSCs and therefore functioned as an osteoblast-specific marker. The second probe aims to monitor osteogenesis, and was generated by conjugating the drug pamidronate to a NIR fluorescent gold nanocluster. Pamidronate specifically binds to hydroxyapatite (HA), a mineral present in bone that is produced by osteoblasts, and therefore provides a functional marker for new bone formation. Our results show that both probes bind to their specific targets in vitro-differentiated osteoblasts, and not to undifferentiated MSCs, and emit NIR fluorescence for functional detection. This in vitro work demonstrates the ability of these probes to bind to active osteoblasts and their mineral deposits and highlight their potential utility as clinical tools for the imaging of the osseointegration process at the molecular level.
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Huesos/diagnóstico por imagen , Colorantes Fluorescentes/farmacología , Imagen Molecular , Osteogénesis/efectos de los fármacos , Desarrollo Óseo/efectos de los fármacos , Huesos/metabolismo , Diferenciación Celular/efectos de los fármacos , Durapatita/metabolismo , Colorantes Fluorescentes/metabolismo , Humanos , Integrina alfa5beta1/química , Integrina alfa5beta1/genética , Células Madre Mesenquimatosas/efectos de los fármacos , Oseointegración/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Pamidronato/farmacología , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: The purpose of this study was to evaluate the feasibility of using proton and sodium magnetic resonance imaging (MRI) to detect fluid accumulation produced by fludrocortisone and nifedipine - two drugs known to cause salt/water retention by different mechanisms. MATERIALS AND METHODS: Twelve young healthy male subjects were randomly assigned to one of two groups and treated with either fludrocortisone or nifedipine for 14 or 25 days, respectively. The change in sodium MRI, as well as in proton T(2) value and T(1)-weighted signal intensity in the calf following postural change [referred to here as 'postural delta signal'(PDS)], was evaluated before, during and after drug administration. The changes in MRI PDS were compared to conventional physiological parameters, including body weight, calf volume and pitting edema. RESULTS: When compared to the baseline pretreatment values, the subjects treated with fludrocortisone showed a 5.5% increase in sodium MRI PDS (P=.01), a 2-ms increase in proton T(2) PDS of the gastrocnemius muscle (P=.06) and a body weight gain of 2.3% (P=.001) within 1 week. In the nifedipine-treated subjects, the sodium MRI PDS increased by 6% versus baseline (P=.03), while the proton T(2) PDS of the gastrocnemius muscle increased by 3.7 ms (P=.01), associated with a 0.5% weight gain (P=.55), within 3 weeks. No significant changes were noted in the T(1)-weighed images following postural change. Measurements of calf circumference, volume and pitting edema did not show consistent changes associated with the drug administration. CONCLUSION: The postural change in sodium MRI and proton T(2) signals provides a sensitive method for detecting the fluid accumulation produced by fludrocortisone and nifedipine. The MRI results are consistent with treatment-induced increases in extracellular fluid volume and correlate well with the observed weight gain. These findings support the potential utility of MRI for the evaluation of medication-induced fluid retention.
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Líquidos Corporales/efectos de los fármacos , Fludrocortisona/farmacología , Pierna , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/metabolismo , Nifedipino/farmacología , Adulto , Humanos , Masculino , Reproducibilidad de los Resultados , Sodio/farmacologíaRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0192047.].
RESUMEN
Epithelial ovarian cancer (EOC) is the seventh most common cancer among women worldwide. The 5-year survival rate for women with EOC is only 30%-50%, which is largely due to the typically late diagnosis of this condition. EOC is difficult to detect in its early stage because of its asymptomatic nature. Recently, near-infrared fluorescent (NIRF) imaging has been developed as a potential tool for detecting EOC at the molecular level. In this study, a NIRF-sensitive probe was designed to detect matrix metalloproteinase (MMP) activity in ovarian cancer cells. A cyanine fluorochrome was conjugated to the amino terminus of a peptide substrate with enzymatic specificity for MMP-3. To analyze the novel MMP-3 probe, an in vivo EOC model was established by subcutaneously implanting SKOV3 cells, a serous-type EOC cell line, in mice. This novel MMP-3-sensitive probe specifically reacted with only the active MMP-3 enzyme, resulting in a significantly enhanced NIRF emission intensity. Histological analysis demonstrated that MMP-3 expression and activity were enhanced in the stromal cells surrounding the ovarian cancer cells. These studies establish a molecular imaging reporter for diagnosing early-stage EOC. Additional studies are required to confirm the early-stage activity of MMP-3 in EOC and its diagnostic and prognostic significance.
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Colorantes Fluorescentes/química , Metaloproteinasa 3 de la Matriz/metabolismo , Imagen Óptica , Neoplasias Ováricas/diagnóstico por imagen , Espectroscopía Infrarroja Corta/métodos , Animales , Línea Celular Tumoral , Técnicas de Cocultivo , Femenino , Xenoinjertos , Humanos , Ratones , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patologíaRESUMEN
BACKGROUND: Individuals who use cocaine have fewer cognitive resources needed to maintain abstinence. This is evidenced by blunted brain function during cognitive control tasks and reduced communication between brain regions associated with cognitive function. For instance, relapse vulnerability is heightened in individuals with less communication between the right and left frontoparietal executive control network (ECN). Given that recent cocaine use enhances such communication, it is plausible that recency of cocaine use influences interhemispheric ECN communication. However, it is unclear whether ECN communication weakens over the course of early cocaine abstinence, which may then enhance relapse risk. METHODS: In ten men with cocaine use disorder, we conducted a preliminary assessment of the relationship between the number of days since last cocaine use (1-3days) and interhemispheric ECN coupling using resting state functional magnetic resonance imaging (fMRI). RESULTS: Reduced interhemispheric ECN coupling was associated with increasing days since last cocaine use; weaker coupling was also associated with lower urine cocaine metabolite concentrations. This association was more prominent in prefrontal than parietal ECN-subregions. CONCLUSIONS: Preliminary results indicate that resting state interhemispheric ECN coupling weakens within the first few days following last cocaine use. Because of the known link between reduced ECN interhemispheric coupling and relapse vulnerability, these results suggest that relapse risk may increase the longer an individual abstains during an early quit attempt. Treatments focused on reversing this coupling deficit may facilitate abstinence.
Asunto(s)
Trastornos Relacionados con Cocaína/fisiopatología , Función Ejecutiva , Vías Nerviosas/fisiopatología , Cocaína/orina , Trastornos Relacionados con Cocaína/orina , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proyectos Piloto , Recurrencia , Síndrome de Abstinencia a Sustancias/fisiopatología , Factores de TiempoRESUMEN
The default mode network (DMN) is a complex dynamic network that is critical for understanding cognitive function. However, whether dynamic topological reconfiguration of the DMN occurs across different brain states, and whether this potential reorganization is associated with prior learning or experience is unclear. To better understand the temporally changing topology of the DMN, we investigated both nodal and global dynamic DMN-topology metrics across different brain states. We found that DMN topology changes over time and those different patterns are associated with different brain states. Further, the nodal and global topological organization can be rebuilt by different brain states. These results indicate that the post-task, resting-state topology of the brain network is dynamically altered as a function of immediately prior cognitive experience, and that these modulated networks are assembled in the subsequent state. Together, these findings suggest that the changing topology of the DMN may play an important role in characterizing brain states.
Asunto(s)
Encéfalo/fisiología , Red Nerviosa/fisiología , Adulto , Mapeo Encefálico , Análisis por Conglomerados , Femenino , Humanos , Masculino , Descanso/fisiología , Análisis y Desempeño de Tareas , Factores de TiempoRESUMEN
Characterization of the default mode network (DMN) as a complex network of functionally interacting dynamic systems has received great interest for the study of DMN neural mechanisms. In particular, understanding the relationship of intrinsic resting-state DMN brain network with cognitive behaviors is an important issue in healthy cognition and mental disorders. However, it is still unclear how DMN functional connectivity links to cognitive behaviors during resting-state. In this study, we hypothesize that static and dynamic DMN nodal topology is associated with upcoming cognitive task performance. We used graph theory analysis in order to understand better the relationship between the DMN functional connectivity and cognitive behavior during resting-state and task performance. Nodal degree of the DMN was calculated as a metric of network topology. We found that the static and dynamic posterior cingulate cortex (PCC) nodal degree within the DMN was associated with task performance (Reaction Time). Our results show that the core node PCC nodal degree within the DMN was significantly correlated with reaction time, which suggests that the PCC plays a key role in supporting cognitive function.
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Atención/fisiología , Giro del Cíngulo/fisiología , Adulto , Mapeo Encefálico/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Vías Nerviosas/fisiología , Pruebas Neuropsicológicas , Tiempo de Reacción , Descanso , Adulto JovenRESUMEN
Impaired brain energy metabolism is among the leading hypotheses in the pathogenesis of affective disorders and linking energy phosphates with states of tissue-function activity is a novel and non-invasive approach to differentiate healthy from unhealthy states. Resting state functional MRI (fMRI) has been established as an important tool for mapping cerebral regional activity and phosphorous chemical shift imaging ((31)P CSI) has been applied to measure levels of energy phosphates and phospholipids non-invasively in order to gain insight into the possible etiology of affective disorders. This is an initial attempt to identify the existence of a correlation between regional energy phosphates and connectivity at nodes of the posterior default mode network (DMN). Resting state fMRI in conjunction with (31)P 2D CSI was applied to 11 healthy controls and 11 depressed patients at 3 T. We found that differences between the two groups exist in correlation of lateral posterior parietal cortex functional connectivity and regional Pi/PCr. Results of this study indicate that resting-state-fMRI-guided (31)P CSI can provide new insight into depression via regional energy phosphates and functional connectivity.