Quantitative Measurement of Joint pH with Magnetic Resonance Imaging

骨关节炎(OA)的诊断基于临床、实验室和影像检查。虽然 诊断成像被广泛应用，通过诊断成像获得的观察结果不一定反映 患者的疼痛体验，这是骨性关节炎临床综合征最重要的表现特征。 事实上，研究估计只有不到50%的膝盖骨关节炎患者报告膝关节疼痛。 骨性关节炎疼痛的决定因素尚不清楚，但涉及多种相互作用的途径。 包括心理社会和生理因素。从生物学角度看，伤害性感觉神经的神经元活动 通路负责信号的产生，在大脑中被解释为疼痛。 多年来，细胞外酸化已被认为是组织中的主要因素。 在痛苦中。质子可以直接激活阳离子通道，如酸敏离子通道(ASIC)，并具有 在过去的二十年里，越来越多的人认识到参与了启动、调制和 疼痛信息的敏感化。事实上，光是酸性环境，不会对组织造成结构性损害，就足以 降低痛觉阈值敏感度，增强疼痛矩阵。 最近，一种独特的分子成像方法，称为酸性CEST磁共振成像(MRI)， 被介绍给了。这种核磁共振成像技术使用临床批准的X射线/计算机断层扫描造影剂作为 利用化学交换饱和转移(CEST)效应测量局部胞外pH。接缝 是酸化CEST技术的理想靶点，因为相对较大的体积和浓度的碘化 在临床关节造影术中，造影剂的使用是常规且安全的。AcidoCEST-UTE序列结合了 用超短回声时间(UTE)采集的ACIDOCEST技术来定量pH敏感的CEST效应 长T2的肌肉骨骼结构(包括软骨、滑膜和肌肉)和短T2的肌肉骨骼结构(包括 半月板、韧带、包膜和肌腱)。一种测量细胞外pH的微创方法可能 潜在地提供了与疼痛有关的化学成分的可视地图。 在我们的第一个目标中，我们寻求优化和加速体模中的酸化技术，并评估 在一系列实验条件下对pH的敏感性。在我们的第二个目标中，我们将我们的技术 适用于将接受全膝关节置换术的患者和无膝关节疼痛的患者。我们假设 我们的技术将提供一种微创的方法来测量细胞外pH，并将提供优越的 ASICs与常规ASICs临床评分及免疫组织化学评价的相关性 结构磁共振成像评价。最终，拟议研究的成功执行将提供以下方面的信息 关节内和关节周围的伤害性系统，使疼痛的内部结构可视化，并促进 临床实践中的诊断和管理决策。

The diagnosis of osteoarthritis (OA) is based on clinical, laboratory, and imaging findings. Although diagnostic imaging is widely practiced, observations gained through diagnostic imaging do not necessarily reflect the patient’s experience of pain, which is the most important presenting feature in the clinical syndrome of OA. In fact, studies have estimated that less than 50% of individuals with radiographic knee OA report knee pain. The determinants of pain in OA are not well understood, but multiple interactive pathways are involved including psycho-social and physical components. From a biological perspective, neuronal activity in nociceptive pathways is responsible for signal generation that is interpreted in the brain as pain. Extracellular acidification in tissues has been recognized for many years now as a major factor involved in pain. Protons can directly activate cation channels, such as acid-sensing ion channels (ASICs), and have become increasingly recognized over the past two decades as being involved in the initiation, modulation, and sensitization of pain messages. In fact, an acidic milieu alone, without structural tissue damage, is sufficient to decrease nociceptor threshold sensitivity and potentiate the pain matrix. Recently, a unique molecular imaging method, termed acidoCEST magnetic resonance imaging (MRI), was introduced. This MRI technique uses a clinically approved X-ray/computed tomography contrast agent as a probe to measure local extra-cellular pH through the chemical exchange saturation transfer (CEST) effect. Joints are ideal targets for the acidoCEST technique since relatively large volumes and concentrations of iodinated contrast are routinely and safely used during clinical arthrography. The acidoCEST-UTE sequence combines the acidoCEST technique with an ultrashort echo time (UTE) acquisition to quantify the pH-sensitive CEST effect in musculoskeletal structures with long T2 (including cartilage, synovium, and muscles) and short T2 (including menisci, ligaments, capsule, and tendons). A minimally-invasive method to measure extracellular pH could potentially provide a visual map of the chemistry involved in pain. In our first aim, we seek to optimize and accelerate the acidoCEST-UTE technique in phantoms and assess sensitivity to pH throughout a range of experimental conditions. In our second aim, we translate our technique to patients who will undergo total knee arthroplasty and to patients without knee pain. We hypothesize that our technique will provide a minimally-invasive method to measure extracellular pH and will provide superior correlations with clinical scores and immunohistochemical evaluation of ASICs compared with conventional structural MRI evaluation. Ultimately, successful execution of the proposed study will provide information on the nociceptive system in and around the joint, enable visualization of painful internal structures, and facilitate diagnostic and management decision-making in clinical practice.