Mapping human brain capillary water lifetime: high‐resolution metabolic neuroimaging

Shutter‐speed analysis of dynamic‐contrast‐agent (CA)‐enhanced normal, multiple sclerosis (MS), and glioblastoma (GBM) human brain data gives the mean capillary water molecule lifetime (τ_b) and blood volume fraction (v_b; capillary density–volume product (ρ^?V)) in a high‐resolution ¹H₂O MRI voxel (40 μL) or ROI. The equilibrium water extravasation rate constant, k_po (τ_b^?1), averages 3.2 and 2.9 s^?1 in resting‐state normal white matter (NWM) and gray matter (NGM), respectively (n = 6). The results (italicized) lead to three major conclusions. (A) k_po differences are dominated by capillary water permeability (P_W^?), not size, differences. NWM and NGM voxel k_po and v_b values are independent. Quantitative analyses of concomitant population‐averaged k_po, v_b variations in normal and normal‐appearing MS brain ROIs confirm P_W^? dominance. (B) P_W^? is dominated (>95%) by a trans(endothelial)cellular pathway, not the P_CA^? paracellular route. In MS lesions and GBM tumors, P_CA^? increases but P_W^? decreases. (C) k_po tracks steady‐state ATP production/consumption flux per capillary. In normal, MS, and GBM brain, regional k_po correlates with literature MRSI ATP (positively) and Na⁺ (negatively) tissue concentrations. This suggests that the P_W^? pathway is metabolically active. Excellent agreement of the relative NGM/NWM k_pov_b product ratio with the literature ³¹PMRSI‐MT CMR_oxphos ratio confirms the flux property. We have previously shown that the cellular water molecule efflux rate constant (k_io) is proportional to plasma membrane P‐type ATPase turnover, likely due to active trans‐membrane water cycling. With synaptic proximities and synergistic metabolic cooperativities, polar brain endothelial, neuroglial, and neuronal cells form “gliovascular units.” We hypothesize that a chain of water cycling processes transmits brain metabolic activity to k_po, letting it report neurogliovascular unit Na⁺,K⁺‐ATPase activity. Cerebral k_po maps represent metabolic (functional) neuroimages. The NGM 2.9 s^?1 k_po means an equilibrium unidirectional water efflux of ~10¹⁵ H₂O molecules s^?1 per capillary (in 1 μL tissue): consistent with the known ATP consumption rate and water co‐transporting membrane symporter stoichiometries. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.     

新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。     

Uterine artery embolization for symptomatic fibroids with imaging follow up

The aim of this study was to determine the effectiveness of uterine artery embolization (UAE) as a primary treatment method in treatment of symptomatic fibroids, whether there are any preembolization MRI characteristics of fibroid predictive of reduction in volume and assess reduction in uterine and dominant fibroid volumes using ultrasound (US) and MRI. Study was carried out in total of 32 patients aged 25–49 years (mean 40.9 years). Uterine and dominant fibroid volume were determined using US and MRI before UAE, MRI and US at 3 months and US alone at 6 and 12 months post‐UAE, supplemented by clinical evaluation at interval of 3, 6 and 12 months. Procedure was carried out through unilateral femoral puncture using poly vinyl alcohol (PVA) particles 355–500 μm in size. All 32 patients had successful procedures. Overall, 25 patients responded, giving a clinical success rate of 78.12%. Mean reduction in volume of uterus and fibroid was 33 and 59.7% and 48.9 and 75.5% on US at 3 and 12 months respectively, and 33.3 and 58.6% on MRI at 3 months. Volume reduction on US and MRI at 3 months was highly correlative. There was no statistical difference in size reduction in volume of fibroids, which were hypointense or hyperintense on T2‐weighted image (T2WI) on pre‐UAE MRI. Uterine artery embolization leads to good technical success and fibroid volume reduction. Ultrasound alone may be used for follow up of patients post‐UAE. Preprocedure signal characteristics on T2WI are not predictors of volume reduction after UAE.     

Using the Anterior Visual System to Assess Neuroprotection and Remyelination in Multiple Sclerosis Trials

Purpose of Review

Clinical trials using agents directed at neuroprotection and remyelination in multiple sclerosis (MS) are needed. As optic neuritis (ON) is common in people with MS and the pathology of ON is similar to other MS lesions in the brain, measurements of the anterior visual system are frequently utilized in neuroprotection and remyelination trials. Understanding the strengths and weaknesses of the measurements is vital when interpreting the results of this research.

Recent Findings

Techniques such as visual evoked potentials (VEP) and optical coherence tomography (OCT) are well established in MS and are thought to measure axonal integrity and myelination. Novel imaging techniques can also be used in conjunction with these measurements to provide better insight into optic nerve structure and function. Magnetization transfer imaging (MTR) together with optic nerve area and volume measures neurodegeneration; diffusion tensor imaging (DTI) measures myelination status and neurodegeneration. However, these techniques require various levels of experience to interpret, and all can be confounded by ocular motion and surrounding fat and bone.

Summary

This article provides a review of established and novel techniques to measure the anterior visual system in multiple sclerosis with a focus on the evidence to support their use as outcome measures in clinical trials focused on neuroprotection and remyelination therapies.

     

Investigating communication in cancer consultations: what can be learned from doctor and patient accounts of their experience?

This study investigated how doctors and patients diagnosed with advanced incurable cancer experienced the disclosure of bad news. The intention was to gain contrasting perspectives of the processes involved in oncology consultations. Sixteen doctors and 16 patients from a cancer centre in the UK participated in the study. A series of consultations were observed and audio recorded, and the perspectives of doctors, patients and relatives were investigated through semi‐structured interviews. Participants were invited to describe how they experienced and felt about the disclosure of information over a period of time following a specific consultation. Analysis was based on a constant comparative method. This research suggests that patients control what they do or do not do with information to meet their own needs and objectives, but doctors do not necessarily appreciate this. Doctors do not always prepare patients for what is happening to them in an active open awareness context, and this can be stressful for some patients. The results indicate that communication is not just about one person making decisions. They also indicate that in many cases more success could be gained from finding out how patients prefer to manage and control the exchange of bad news, at different points, through their care pathway.