Title: Physiology of Inflammatory Arthritis in High Resolution Abstract Development of new imaging technologies to identify and validate biomarkers of inflammatory arthritic disease is of broad interest and aligned with common goals of physicians, medical researchers, and scientific entities. Presenting highly sensitive optical information in subsurface tissue with spatial resolution comparable to ultrasound (US) imaging, the emerging photoacoustic (PA) imaging offers significant advantages to early diagnosis and prognosis, as well as assessing the treatment of arthritis, by providing additional new functional information about the disease activity that can be effectively combined with more established and widely accepted musculoskeletal US imaging. Our current research on arthritis patients has successfully demonstrated that a combined US-PA system is capable of identifying and characterizing inflammation in human peripheral joints, based on the detection of hemodynamic and metabolic changes, including both hyperemia and hypoxia. These are important and early physiological biomarkers of synovitis reflecting the increased metabolic demand and the relatively inadequate oxygen delivery of the inflammatory synovial tissue. Encouraged by the initial success of our study on arthritis patients, we propose to further advance the translation of US-PA dual imaging technology to clinical management of inflammatory arthritis. Our ultimate goal is to develop a cost-efficient and point-of-care joint imaging device that can enable early treatment modification and personalized medicine, changing the current procedures in rheumatology clinic. In this research, to understand the clinical value of the proposed imaging technology, we will identify a group of robust, reliably reproducible, and precise biomarkers that can reflect the early pathological changes of inflammatory arthritis and its response to treatment. The central hypothesis is that a group of 3D US and PA biomarkers that can be evaluated by the proposed imaging technology can lead to better assessment of arthritis disease state and treatment response than those evaluated by conventional 2D US imaging. To examine this hypothesis, following specific aims will be accomplished:
Aim 1 : Develop a method to assess inflammatory arthritis disease activity by quantifying 3D US and PA biomarkers that reflect the underlying pathological condition of specific joints Aim 2: Evaluate the performance of these biomarkers in assessing the pathological condition in local joints affected by arthritis through the study on a well-developed animal model Aim 3. Evaluate the clinical value of the identified imaging biomarkers that can be assessed by the US-PA dual-modality technology via a pilot study on patients affected by inflammatory arthritis

Public Health Relevance

We propose to develop a 3D automated ultrasound (US) and photoacoustic (PA) dual imaging system for early detection and treatment assessment of human inflammatory arthritis. To examine the value of this novel imaging technology to rheumatology clinic, a group of US and PA biomarkers that reflect early pathological changes in arthritic joint and its response to therapy will be studied via the experiments on an animal model and human subjects.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Lester, Gayle E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Engineering (All Types)
Schools of Medicine
Ann Arbor
United States
Zip Code
Hu, Zizhong; Zhang, Haonan; Mordovanakis, Aghapi et al. (2017) High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation. Sci Rep 7:40243
Jo, Janggun; Xu, Guan; Cao, Meng et al. (2017) A Functional Study of Human Inflammatory Arthritis Using Photoacoustic Imaging. Sci Rep 7:15026
Zhang, Haonan; Chao, Wan-Yu; Cheng, Qian et al. (2017) Interstitial photoacoustic spectral analysis: instrumentation and validation. Biomed Opt Express 8:1689-1697
Xu, Guan; Xue, Yafang; Özkurt, Zeynep Gürsel et al. (2017) Photoacoustic imaging features of intraocular tumors: Retinoblastoma and uveal melanoma. PLoS One 12:e0170752
Xu, Guan; Qin, Ming; Mukundan, Ananya et al. (2016) Prostate cancer characterization by optical contrast enhanced photoacoustics. Proc SPIE Int Soc Opt Eng 9708:
Lei, Hao; Johnson, Laura A; Liu, Shengchun et al. (2016) Characterizing intestinal inflammation and fibrosis in Crohn's disease by photoacoustic imaging: feasibility study. Biomed Opt Express 7:2837-48
Tian, Chao; Qian, Wei; Shao, Xia et al. (2016) Plasmonic Nanoparticles with Quantitatively Controlled Bioconjugation for Photoacoustic Imaging of Live Cancer Cells. Adv Sci (Weinh) 3:1600237
Keswani, Rahul K; Tian, Chao; Peryea, Tyler et al. (2016) Repositioning Clofazimine as a Macrophage-Targeting Photoacoustic Contrast Agent. Sci Rep 6:23528
Xu, Guan; Meng, Zhuo-Xian; Lin, Jian-Die et al. (2016) High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy. Sci Rep 6:16937
Tian, Chao; Feng, Ting; Wang, Cheng et al. (2016) Non-Contact Photoacoustic Imaging Using a Commercial Heterodyne Interferometer. IEEE Sens J 16:8381-8388

Showing the most recent 10 out of 35 publications