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，实验室和成像结果。虽然 诊断成像是广泛实践的，通过诊断成像进行观察不一定反映 患者的疼痛经历，这是OA临床综合征中最重要的表现特征。 实际上，研究估计，射线照相膝关节OA的个体中只有不到50％的人报告膝盖疼痛。 OA中疼痛的决定者尚不清楚，但涉及多种互动途径 包括心理社会和身体成分。从生物学的角度来看，伤害感受性的神经元活性 途径负责在大脑中解释为疼痛的信号产生。 多年来，组织中的细胞外酸化已被认为是涉及的主要因素 痛苦。质子可以直接激活阳离子通道，例如酸敏离子通道（ASIC），并具有 在过去的二十年中，人们越来越认识到参与主动性，调制和 疼痛消息的敏化。实际上，仅一个没有结构性组织损伤的酸性环境就足以 减少伤害感受器阈值灵敏度并潜在疼痛矩阵。 最近，一种独特的分子成像方法，称为酸根磁共振成像（MRI）， 该MRI技术使用经过临床批准的X射线/计算机断层扫描剂作为一个 探测通过化学交换安全转移（CEST）效应测量局部细胞外pH。关节 是酸索技术的理想目标，因为相对较大的体积和浓度 对比度在临床关节造影期间通常可安全地使用。酸索ute序列结合了 具有超短回声时间（UTE）采集的酸索技术，以量化pH敏感的CEST效应 肌肉骨骼结构，具有长T2（包括软骨，滑膜和肌肉）和短T2（包括 半月板，韧带，胶囊和肌腱）。测量细胞外pH的最小侵入性方法 有可能提供涉及疼痛的化学反应的视觉图。 在我们的第一个目标中，我们试图在幻影和评估中优化和加速酸蛋糕技术 在一系列实验条件下对pH的敏感性。在第二个目标中，我们翻译了技术 对于那些将接受全膝关节置换术和没有膝盖疼痛的患者的患者。我们假设这一点 我们的技术将提供一种最小的侵入性方法来测量细胞外pH，并将提供优质 与常规 结构MRI评估。最终，拟议研究的成功执行将提供有关 关节内外的伤害性系统，使内部结构可视化，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