In Vivo Viscoelastic Response (VisR) Ultrasound for Characterizing Mechanical Anisotropy in Lower-Limb Skeletal Muscles of Boys with and without Duchenne Muscular Dystrophy

Our group has previously found that in silico, mechanical anisotropy may be interrogated by exciting transversely isotropic materials with geometrically asymmetric acoustic radiation force excitations and then monitoring the associated induced displacements in the region of excitation. We now translate acoustic radiation force-based anisotropy assessment to human muscle in vivo and investigate its clinical relevance to monitoring muscle degeneration in Duchenne muscular dystrophy (DMD). Clinical anisotropy assessments were performed using Viscoelastic Response ultrasound, with a degree of anisotropy reflected by the ratios of Viscoelastic Response relative elasticity (RE) or relative viscosity (RV) measured with the asymmetric radiation force oriented parallel versus perpendicular to muscle fiber alignment. In vivo results from rectus femoris and gastrocnemius muscles of boys aged ～7.9–10.4 y indicate that RE and RV anisotropy ratios in rectus femoris muscles of boys with DMD were significantly higher than those of healthy control boys (RE: DMD?=?1.51 ± 0.87, control?=?0.99 ± 0.69, p?=?0.04, Wilcoxon rank sum test; RV: DMD?=?1.04 ± 0.71, control?=?0.74 ± 0.22, p?=?0.02). In the gastrocnemius muscle, only the RV anisotropy ratio was significantly higher in dystrophic than control patients (DMD?=?1.23 ± 0.35, control?=?0.88 ± 0.31, p?=?0.04). In the dystrophic rectus femoris muscle, the RE anisotropy ratio was inversely correlated (slope?=?–0.03/lbf, r?=?–0.43, p?=?0.07, Pearson correlation) with quantitative muscle testing functional output measures but was not correlated with quantitative muscle testing in the dystrophic gastrocnemius. These results suggest that Viscoelastic Response RE and RV measures reflect differences in mechanical anisotropy associated with functional impairment with dystrophic degeneration that are relevant to monitoring DMD clinically.     

Effects of various direct or indirect dopamine agonists on the latency of the acoustic startle response in rats

Summary The effects of dopamine agonists were investigated on the latency of the acoustic startle response in male Wistar rats. Four indirect dopamine agonits were tested: GBR 12783 (5–20mg/kg), BTCP (5–20mg/kg), dexamphetamine (3–6mg/kg) and L-DOPA 100 mg/kg associated with benserazide 25 mg/kg; they induced an increase in startle latency. Apomorphine at a dose (50 g/kg) known to decrease dopaminergic transmissions, was ineffective on the startle response. On the contrary, at 0.6 or 2 mg/kg, apomorphine induced an increase in the startle latency. A similar effect was observed with bromocriptine at 10 mg/kg from the 10th min up to at least the 9th hour after treatment. The specific agonist of D2 receptors Ru 24926 (0.45 mg/kg) enhanced the startle latency as well as the specific agonist of D1 receptors SKF 38393 (10 mg/kg). The association of these drugs resulted in an apparent additivity of their individual effects. The effect of apomorphine (0.6 mg/kg) was only partially reduced by a high dose of the specific D2 antagonist amisulpride (80 mg/kg) and more clearly antagonized by the specific D1 antagonist SCH 23390 (50 g/kg). It is concluded that D2 and D1 receptors contribute to the increase in startle latency elicited by direct or indirect dopamine agonists.     

Cortical circumferential profile of SPECT cerebral perfusion in Alzheimer''s disease

We developed a semiautomatic method termed “cortical circumferential profiling” for objective analysis of cerebral cortex function in emission tomographic neuroimaging studies. This method treats cortex as a continuous ring near the outer brain edge. A computer algorithm samples the cortex at 60 contiguous, equiangular locations, using 1-cm² samples. These values are plotted as a function of cortical angle to produce the cortical circumferential profile. This method was used in a study of regional cerebral perfusion in 15 patients with Alzheimer's disease and 8 elderly control subjects using N-isopropyl [I-123]-iodoamphetamine. Cortical circumferential profiling decreases variability, examines the entire cortex within slices at preselected levels above the orbital-meatal line, and facilitates intrasubject and intersubject comparisons.     

Synaptic analysis of amacrine cells with neuropeptide Y-like immunoreactivity in turtle retina

Neuropeptide Y-like immunoreactivity has been localized previously within three classes of amacrine cells in the turtle retina. We have used the avidin-biotin with horseradish peroxidase technique to label these neurons for examination at the ultrastructural level to answer the following questions. Where are the synaptic contacts of these neurons made? What types of neurons are involved pre- and postsynaptically? What is the intracellular distribution of the immunoreactivity? Processes with neuropeptide Y-like immunoreactivity were located primarily within three regions of the inner plexiform layer: stratum 1, stratum 3, and at the border between strata 4 and 5. In all three regions the processes with neuropeptide Y-like immunoreactivity received synaptic contacts from both unlabeled amacrine and bipolar cells, but the majority of the synaptic input in all three regions was from unlabeled amacrine cells. Processes with neuropeptide Y-like immunoreactivity were presynaptic to unlabeled amacrine cells in all three regions, but also formed contacts onto unlabeled bipolar cells in the region between strata 4 and 5. The immunoreactivity within these cells gave rise to a diffuse reaction product that was distributed throughout the cytoplasm and within large vesicles. This localization of neuropeptide Y-like immunoreactivity within large vesicles suggests that this peptide may play a neuromodulatory role. Such a role would be consistent with previous studies of neuropeptides in the turtle retina.     

HL-1改变兔肝脏组织声学环境的实验研究(Ⅰ)

目的　探讨HL -1改变兔肝脏组织声学环境的作用及机制。方法　实验组经兔耳缘静脉输入HL -1,B超实时监测 0min ,2min ,5min ,10min ,15min和 2 0min兔肝脏的声像图。对照组以生理盐水代替HL -1,余步聚同实验组。实验后两组兔肝脏送组织病理检查。结果　实验组兔肝脏BUGs随HL -1的输入而迅速下降 ,至 15～ 2 0min时达最低值 ( -12 .90± 2 .5 3 ) ;对照组稍有增加 ( 1.43± 1.90 )。大体观实验组兔肝脏呈粉红色 ,可见类似脂肪肝似的脂质沉着 ;病理检查肝细胞增大、肿胀、肝索排列紊乱 ,肝血窦腔隙及中央静脉缩小 ,肝细胞及肝血窦内见大量脂质体沉积 ,位于血窦的脂质体有聚积现象 ,与对照组肝脏有明显差异。结论　静脉快速输入HL -1可使兔肝脏组织结构发生相应的变化 ,使肝脏声吸收衰减增加 ,因而改变了肝脏组织声学环境     

Predictive value of Kushida index and acoustic pharyngometry for the evaluation of upper airway in subjects with or without obstructive sleep apnea

Acoustic pharyngometry is a relatively new noninvasive method that quantifies geometrically complexed pharyngeal dimensions. Our study aimed to investigate the predictability and usefulness of acoustic pharyngometry in diagnosis of obstructive sleep apnea (OSA), and we developed a prospective clinical trial in 16 subjects without apnea and 54 subjects with apnea. All seventy subjects received polysomnography (PSG) to assess the sleep architecture, including breathing and the degree of apnea hypopnea index. Acoustic pharyngometry was performed in four body positions (sitting, supine, right and left lateral) while awake with tidal breathing in addition to morphometric measurements (Kushida index) of oral cavity. This study shows that the cross-sectional area and volume of the upper airway is smaller in the supine position than any other positions. As well, the oropharyngeal junction area of the supine position is the most predictive parameter to discriminate between subjects with or without OSA. Acoustic pharyngometry can be a clinically useful tool for localizing the narrowed portion of the upper airway and predicting obstructive sleep apnea.     

On the use of R1 and R2* for measurement of contrast agent concentration in isolated perfused rat liver

We present experimental MRI protocols at 4.7 T for quantitative determination of the Dotarem distribution volume in isolated perfused rat liver. The procedures involved either constant contrast agent (CA) concentration or bolus administration conditions. R1 and R2* effects of the CA in liver and perfusate were measured using gradient echo fast imaging (GEFI) experiments by varying either the excitation angle or the echo time. CA concentrations in liver and perfusate were also measured after MRI by inductively coupled plasma atomic emission spectroscopy, in order to determine in situ relaxivities in the perfusate (r1=4.2 +/- 0.1 s(-1) mm(-1), r2*=17 +/- 2 s(-1) mm(-1)) and in the liver (r1=7.2 +/- 0.2 s(-1) mm(-1), r2*=99 +/- 5 s(-1) mm(-1)). When CA concentrations were estimated from R1 measurements and r1, the CA distribution volume estimations in liver resulting from bolus (0.31 +/- 0.01) and stationary (0.32 +/- 0.05) experiments were not significantly different. In contrast, after a bolus, CA concentrations derived from R2* and r2* were overestimated in liver and even more in perfusate. However, with R1 and R2* being measured before CA bolus administration, zero echo time signal intensities computed from multiple TE measurements during multiple boli yielded good estimations of R1 and thus correct CA concentrations in liver and in perfusate. Under these conditions, a single multi-echo GEFI acquisition should be sufficient to determine the concentration-time curves. Consequently, this protocol should be appropriate to rapidly estimate the distribution volume in vivo when multiple boli have to be avoided.     

Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopy

Absolute quantitative measures of breast cancer tissue metabolites can increase our understanding of biological processes. Electronic REference To access In vivo Concentrations (ERETIC) was applied to high resolution magic angle spinning MR spectroscopy (HR MAS MRS) to quantify metabolites in intact breast cancer samples. The ERETIC signal was calibrated using solutions of creatine and TSP. The largest relative errors of the ERETIC method were 8.4%, compared to 4.4% for the HR MAS MRS method using TSP as a standard. The same MR experimental procedure was applied to intact tissue samples from breast cancer patients with clinically defined good (n = 13) and poor (n = 16) prognosis. All samples were examined by histopathology for relative content of different tissue types and proliferation index (MIB‐1) after MR analysis. The resulting spectra were analyzed by quantification of tissue metabolites (β‐glucose, lactate, glycine, myo‐inositol, taurine, glycerophosphocholine, phosphocholine, choline and creatine), by peak area ratios and by principal component analysis. We found a trend toward lower concentrations of glycine in patients with good prognosis (1.1 µmol/g) compared to patients with poor prognosis (1.9 µmol/g, p = 0.067). Tissue metabolite concentrations (except for β‐glucose) were also found to correlate to the fraction of tumor, connective, fat or glandular tissue by Pearson correlation analysis. Tissue concentrations of β‐glucose correlated to proliferation index (MIB‐1) with a negative correlation factor (?0.45, p = 0.015), consistent with increased energy demand in proliferating tumor cells. By analyzing several metabolites simultaneously, either in ratios or by metabolic profiles analyzed by PCA, we found that tissue metabolites correlate to patients' prognoses and health status five years after surgery. This study shows that the diagnostic and prognostic potential in MR metabolite analysis of breast cancer tissue is greater when combining multiple metabolites (MR Metabolomics). Copyright © 2010 John Wiley & Sons, Ltd.