Quantitative Measurement of Joint pH with Magnetic Resonance Imaging

利用磁共振成像定量测量关节 pH 值

• 批准号: 10543400
• 负责人: Eric Y Chang
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10543400
• 关键词: 3-Dimensional; ASIC channel; Address; Arthralgia; Arthritis; Arthrography; Biological; Brain; Cartilage; Cations; Chemicals; Chemistry; Chronic; Clinic; Clinical; Contrast Media; Control Groups; Decision Making; Degenerative polyarthritis; Diagnosis; Diagnostic; Diagnostic Imaging; Electrodes; Evaluation; General Population; Generations; Goals; Healthcare Systems; Histology; Image; Image Analysis; Imaging Techniques; Individual; Joints; Knee Osteoarthritis; Knee joint; Laboratories; Ligaments; Location; Magnetic Resonance Imaging; Measurement; Measures; Meniscus structure of joint; Methods; Muscle; Musculoskeletal structure; Neurons; Nociception; Nociceptors; Operative Surgical Procedures; Pain; Pathway interactions; Patient Self-Report; Patients; Peripheral; Physiological; Protons; Reference Standards; Reporting; Signal Transduction; Structural defect; Structure; Surface; Symptoms; Syndrome; Synovial Membrane; Synovitis; System; Techniques; Temperature; Tendon structure; Time; Tissues; Translating; Veterans; Visualization; Western Ontario and McMaster Universities Arthritis Index; X-Ray Computed Tomography; base; capsule; chronic pain; clinical practice; cohort; disability; experience; extracellular; imaging modality; in vivo; knee pain; knee replacement arthroplasty; meniscal tear; military veteran; minimally invasive; molecular imaging; osteochondral tissue; pain perception; psychosocial; radiological imaging; visual map

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.

骨关节炎 (OA) 的诊断基于临床、实验室和影像学检查结果。 诊断成像已广泛应用，但通过诊断成像获得的观察结果并不一定反映 患者的疼痛体验是 OA 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% 的放射学膝关节 OA 患者报告膝关节疼痛。 骨关节炎疼痛的决定因素尚不清楚，但涉及多种相互作用途径 从生物学角度来看，伤害感受的神经活动包括心理社会和身体成分。 这些通路负责产生信号，这些信号在大脑中被解释为疼痛。 多年来，组织中的细胞外酸化已被认为是一个主要因素 在疼痛中，质子可以直接激活阳离子通道，例如酸敏感离子通道（ASIC），并且具有 在过去的二十年中，人们越来越认识到其参与启动、调节和 事实上，在没有结构组织损伤的情况下，仅酸性环境就足以使疼痛信息变得敏感。 降低伤害感受器阈值敏感性并增强疼痛基质。 最近，一种独特的分子成像方法，称为 AcidoCEST 磁共振成像 (MRI)， 该 MRI 技术使用临床认可的 X 射线/计算机断层扫描造影剂作为造影剂。 探针通过化学交换饱和转移 (CEST) 效应测量局部细胞外 pH 值。 是 AcidoCEST 技术的理想目标，因为碘化物的体积和浓度相对较大 对比剂在临床关节造影中常规且安全地使用 AcidoCEST-UTE 序列结合了 AcidoCEST 技术采用超短回波时间 (UTE) 采集来量化 pH 敏感的 CEST 效应 长T2（包括软骨、滑膜和肌肉）和短T2（包括 一种测量细胞外 pH 值的微创方法可以实现。 可能提供与疼痛有关的化学物质的视觉图。 在我们的第一个目标中，我们寻求优化和加速体模中的 AcidoCEST-UTE 技术并评估 我们的第二个目标是转化我们的技术。 将接受全膝关节置换术的患者以及没有膝关节疼痛的患者。 我们的技术将提供一种微创方法来测量细胞外 pH 值，并将提供卓越的 与传统方法相比，ASIC 与临床评分和免疫组织化学评估的相关性 最终，拟议研究的成功执行将提供有关结构的信息。 关节内和周围的伤害感受系统，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。

项目成果

Quantitative three-dimensional ultrashort echo time cones imaging of the knee joint with motion correction.

具有运动校正的膝关节定量三维超短回波时间锥成像。

• DOI: 10.1002/nbm.4214
• 发表时间: 2020
• 期刊: NMR in biomedicine
• 影响因子: 2.9
• 作者: Wu,Mei;Zhao,Wei;Wan,Lidi;Kakos,Lena;Li,Liang;Jerban,Saeed;Jang,Hyungseok;Chang,EricY;Du,Jiang;Ma,Ya-Jun
• 通讯作者: Ma,Ya-Jun

Interpretation of Cartilage Damage at Routine Clinical MRI: How to Match Arthroscopic Findings.

• DOI: 10.1148/rg.220051
• 发表时间: 2022-08
• 期刊: Radiographics : a review publication of the Radiological Society of North America, Inc
• 作者: B. Markhardt;Brady K. Huang;Andrea M. Spiker;E. Chang

Rapid single scan ramped hybrid-encoding for bicomponent T2* mapping in a human knee joint: A feasibility study.

• DOI: 10.1002/nbm.4391
• 发表时间: 2020-11
• 期刊: NMR in biomedicine
• 影响因子: 2.9
• 作者: Jang H;McMillan AB;Ma Y;Jerban S;Chang EY;Du J;Kijowski R
• 通讯作者: Kijowski R

Fast quantitative three-dimensional ultrashort echo time (UTE) Cones magnetic resonance imaging of major tissues in the knee joint using extended sprial sampling.

• DOI: 10.1002/nbm.4376
• 发表时间: 2020-10
• 期刊: NMR in biomedicine
• 影响因子: 2.9
• 作者: Wan L;Ma Y;Yang J;Jerban S;Searleman AC;Carl M;Le N;Chang EY;Tang G;Du J
• 通讯作者: Du J

The prognostic and diagnostic value of 18F-FDG PET/CT for assessment of symptomatic osteoarthritis.

18F-FDG PET/CT 对评估症状性骨关节炎的预后和诊断价值。

• DOI: 10.1097/mnm.0000000000000858
• 发表时间: 2018
• 期刊: Nuclear medicine communications
• 影响因子: 1.5
• 作者: Nguyen,BrianJ;Burt,Ashley;Baldassarre,RandallL;Smitaman,Edward;Morshedi,Maud;Kao,Steven;Chang,EricY;Obrzut,Sebastian
• 通讯作者: Obrzut,Sebastian