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。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OA临床综合征中最重要的表现特征。 事实上，研究估计不到50%的放射学膝关节OA患者报告膝关节疼痛。 OA疼痛的决定因素尚不清楚，但涉及多种相互作用的途径 包括心理社会和身体方面的因素。从生物学的角度来看，伤害性感受中的神经元活动 神经通路负责产生在大脑中被解释为疼痛的信号。 多年来，组织中的细胞外酸化已被认为是一个主要因素 很痛苦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 在过去的二十年里，越来越多的人认识到， 疼痛信息的敏感性。事实上，在没有结构性组织损伤的情况下，单独的酸性环境足以 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）， 出台这种MRI技术使用临床批准的X射线/计算机断层扫描造影剂作为 探针通过化学交换饱和转移（CEST）效应测量局部细胞外pH。关节 是acidoCEST技术的理想靶点，因为相对大体积和浓度的碘化 造影剂在临床关节造影术期间常规且安全地使用。acidoCEST-UTE序列结合了 采用超短回波时间（UTE）采集的acidoCEST技术，以量化 具有长T2（包括软骨、滑膜和肌肉）和短T2（包括 韧带、关节囊和肌腱）。一种测量细胞外pH值的微创方法可以 潜在地提供了疼痛中所涉及的化学物质的视觉地图。 在我们的第一个目标中，我们寻求优化和加速phantomy中的acidoCEST-UTE技术，并评估 在整个实验条件范围内对pH的敏感性。在我们的第二个目标中， 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值，并将提供上级 与常规ASICs相比，ASICs与临床评分和免疫组化评价的相关性 结构MRI评价。最终，拟议研究的成功执行将提供以下信息： 关节内和关节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

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

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

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

MRI-based mechanical competence assessment of bone using micro finite element analysis (micro-FEA): Review.

• DOI: 10.1016/j.mri.2022.01.009
• 发表时间: 2022-05
• 期刊: Magnetic resonance imaging
• 影响因子: 2.5
• 作者: Jerban S;Alenezi S;Afsahi AM;Ma Y;Du J;Chung CB;Chang EY
• 通讯作者: Chang EY