Imaging of joints with laser-based photoacoustic tomography: An animal study Xueding Wang a Department of Radiology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 David L. Chamberland b Division of Rheumatology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 Paul L. Carson, J. Brian Fowlkes, Ronald O. Bude, and David A. Jamadar Department of Radiology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 Blake J. Roessler Division of Rheumatology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 Received 17 March 2006; revised 3 May 2006; accepted for publication 25 May 2006; published 12 July 2006 Photoacoustic tomography PAT, a nonionizing, noninvasive, laser-based technology was adapted to joint imaging for the first time. Pulsed laser light in the near-infrared region was directed toward a joint with resultant ultrasonic signals recorded and used to reconstruct images that present the optical properties in subsurface joint tissues. The feasibility of this joint imaging system was validated on a Sprague Dawley rat tail model and verified through comparison with histology. With sufficient penetration depth, PAT realized tomographic imaging of a joint as a whole organ nonin- vasively. Based on the optical contrast, various intra- and extra-articular tissues, including skin, fat, muscle, blood vessels, synovium and bone, were presented successfully in images with satisfactory spatial resolution that was primarily limited by the bandwidth of detected photoacoustic signals rather than optical diffusion as occurs in traditional optical imaging. PAT, with its intrinsic advan- tages, may provide a unique opportunity to enable the early diagnosis of inflammatory joint disor- ders, e.g., rheumatoid arthritis, and to monitor therapeutic outcomes with high sensitivity and accuracy. © 2006 American Association of Physicists in Medicine. DOI: 10.1118/1.2214166 Key words: photoacoustic tomography, inflammatory arthritis, joints I. INTRODUCTION Inflammatory arthritis encompasses many pathological rheu- matic diseases including rheumatoid arthritis RA and se- ronegative spondyloarthropathies. RA, the most common form of inflammatory arthritis, is a systemic disease pre- dominantly manifested in the synovial membrane of diar- throdial joints. 1 About 1% of the population is affected by RA and 80% of the patients are disabled after 20 years. 2 The synovium affected by RA is marked by neovascularization, inflammatory cell infiltration, and associated synoviocyte hyperplasia. 3 Synovial membrane inflammation is one of the earliest pathologic changes in RA and other inflammatory joint diseases. Because the enhanced blood vessel growth contributes to the inflammatory joint destruction, inflamma- tory arthritis is now widely regarded as an angiogenesis- dependent disease. 4–7 Despite the hypervascularization, the rheumatic synovium appears to be a relatively hypoxic envi- ronment caused by an imbalance between local metabolic rate and synovial vascular supply. 8–11 Implementing effective treatments for patients with in- flammatory arthritis, i.e., early initiation and optimal adjust- ments of therapies, requires technologies for early diagnosis and highly sensitive monitoring of disease progression. 12 Driven by clinical investigations looking for optimized thera- pies and pharmaceutical industries searching for new drugs, musculoskeletal imaging is playing an increasingly impor- tant role in the diagnosis, assessment and monitoring of ar- thritis. Recent advances in joint imaging, including magnetic resonance imaging MRI 13,14 and ultrasonography, 15–17 have added objective data enhancing diagnosis and treatment monitoring of these diseases. However, identification of ini- tial natural disease sequelae, early diagnosis, and pharmaceu- tical based intervention and disease progression monitoring still present challenges. Recently, nonionizing optical modalities for imaging and sensing of joint diseases have drawn considerable attention. Optical imaging of biological tissues is highly desirable be- cause of known intrinsic optical contrast that is sensitive to tissue abnormalities and function. Optical properties of tissue in the visible and near-infrared NIR region of the electro- magnetic spectrum can demonstrate the molecular constitu- ents of tissues and the electronic or vibrational structures at the molecular scale. Similar to tumors, the hallmarks of rheu- matic joint tissues include angiogenesis, hypervasculariza- tion, hypermetabolism, hypoxia, and invasion into normal adjacent tissues. Optical properties may be used to quantify these morphological and physiological changes and, conse- quently, potentially enable the early diagnosis of inflamma- 2691 2691 Med. Phys. 33 „8…, August 2006 0094-2405/2006/33„8…/2691/7/$23.00 © 2006 Am. Assoc. Phys. Med.