RESUMEN
The serotonin transporter-linked promoter region (5-HTTLPR) polymorphism of the serotonin transporter gene is associated with amygdala response during negative emotion. The aim of this study was to investigate whether this genotype effect on amygdala function is mediated by current serotonin transporter (5-HTT) levels or rather by genetically induced influences during neurodevelopment, shaping brain structure. A total of 54 healthy subjects underwent functional and structural magnetic resonance imaging, [(11)C]DASB positron emission tomography and 5-HTTLPR genotyping to analyze the interrelationships between amygdala activation during processing of unpleasant stimuli, 5-HTTLPR genotype, amygdala volumes and 5-HTT levels in the midbrain and in other brain regions. In line with previous research, carriers of the short allele (S) showed increased amygdala activation. Path analysis demonstrated that this genotype effect was not procured by current 5-HTT availability but by amygdala structure, with smaller amygdala volumes in the S than in the LL genotype, as well as smaller volumes being associated with increased amygdala activation. Our findings stress the role of genetic effects during neurodevelopment.
Asunto(s)
Amígdala del Cerebelo/fisiología , Polimorfismo Genético/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Amígdala del Cerebelo/metabolismo , Femenino , Regulación de la Expresión Génica/genética , Técnicas de Genotipaje , Humanos , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Proteínas de Transporte de Serotonina en la Membrana Plasmática/biosíntesis , Proteínas de Transporte de Serotonina en la Membrana Plasmática/fisiología , Fumar/psicologíaRESUMEN
BACKGROUND AND PURPOSE: Brains of patients with multiple sclerosis (MS) characteristically have "black holes" (BHs), hypointense lesions on T1-weighted (T1W) spin-echo (SE) images. Although conventional MR imaging can disclose chronic BHs (CBHs), it cannot stage the degree of their pathologic condition. Tissue-specific imaging (TSI), a recently introduced MR imaging technique, allows selective visualization of white matter (WM), gray matter (GM), and CSF on the basis of T1 values of classes of tissue. We investigated the ability of TSI-CSF to separate CBHs with longer T1 values, which likely represent lesions containing higher levels of destruction and unbound water. MATERIALS AND METHODS: Eighteen patients with MS, who had already undergone MR imaging twice (24 months apart) on a 1.5T scanner, underwent a 3T MR imaging examination. Images acquired at 1.5T included sequences of precontrast and postcontrast T1W SE, T2-weighted (T2W) SE, and magnetization transfer (MT). Sequences obtained at 3T included precontrast and postcontrast T1W SE, T2W SE, T1 inversion recovery prepared fast spoiled gradient recalled-echo (IR-FSPGR) and TSI. A BH on the 3T-IR-FSPGR was defined as a CBH if seen as a hypointense, nonenhancing lesion with a corresponding T2 abnormality for at least 24 months. CBHs were separated into 2 groups: those visible as hyperintensities on TSI-CSF (group A), and those not appearing on the TSI-CSF (group B). RESULTS: Mean MT ratios of group-A lesions (0.22 +/- 0.06, 0.13-0.35) were lower (F(1,13) = 60.39; P < .0001) than those of group-B lesions (0.32 +/- 0.03, 0.27-0.36). CONCLUSIONS: Group-A lesions had more advanced tissue damage; thus, TSI is a potentially valuable method for qualitative and objective identification.
Asunto(s)
Algoritmos , Encéfalo/patología , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Esclerosis Múltiple/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Interferon beta (IFN-beta) is among the first-line treatment options for patients with multiple sclerosis (MS). A potential caveat of therapy, however, is the development of neutralizing antibodies (NAb) and/or neutralizing activity (NA) non-antibody mediated, although debate is still ongoing as to whether NAb significantly hampers the efficacy of the drug or rather represents an immunologically irrelevant epiphenomenon. In the present study, we describe the effect of NAb on IFN-beta-1b through clinical and magnetic resonance imaging (MRI) outcome measures of five relapsing-remitting multiple sclerosis (RRMS) patients who were treated with 250 mug of subcutaneously administered IFN-beta-1b every other day and developed NAb at varying titres and times during the course of therapy. Despite the small number of NAb(+) patients, heterogeneity in MRI/clinical response to IFN-beta-1b was identified. Response to IFN-beta-1b therapy was observed in the absence or presence of NAb. Also observed was failure to IFN-beta-1b coincident with high and sustained NAb titres, but also before NAb development or in the presence of low NAb titres. Multiple MRI and NAb measurements performed within the same individual allow for a better description of the complex heterogeneous response to IFN-beta-1b with respect to NAb occurrence.
Asunto(s)
Anticuerpos/sangre , Interferón beta/inmunología , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Encéfalo/patología , Femenino , Estudios de Seguimiento , Humanos , Interferon beta-1b , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/patología , Resultado del TratamientoRESUMEN
Selective excitation pulses are widely used in magnetic resonance imaging in order to excite predetermined slices of the body under examination. Such pulses are optimally designed by means of the Shinnar-Le Roux algorithm. In this paper, we show that under minimal assumptions, the complexity and computing cost of the original Shinnar-Le Roux algorithm can be drastically reduced. We further propose an improved version of the algorithm, involving only real quantities, which is both easier to implement and faster to execute, so it is suitable for implementation at the hardware level, in the context of a real-time fully digital magnetic resonance transceiver.