Current imaging strategies in rheumatoid arthritis

Abstract

As remission has now become a realistic therapeutic goal in the clinical management of RA due to the introduction and widespread adoption of biologic agents, there is a greater need for earlier diagnoses and objective methods for evaluating disease activity and response to treatment. In this capacity, advanced imaging strategies are assuming an expansive clinical role, particularly as they take advantage of newer imaging technologies and the shift toward imaging at the molecular level. Molecular imaging utilizes target-specific probes to non-invasively visualize molecular, cellular, and physiological perturbations in response to the underlying pathology. Probes for nuclear and MR imaging have been and are being developed that react with discrete aspects of inflammatory and destructive pathways specific to RA. These probes in addition to new MR sequences and contrast agents have the potential to provide an earlier and more reliable assessment of clinical outcome, disease activity, severity, and location, and therapeutic response. Furthermore, these imaging strategies may enable a more fundamental understanding of critical pathophysiological processes and the advent of new molecular therapies. This review will discuss these advances in both nuclear medicine and MRI strategies for imaging RA with a particular emphasis on molecular imaging.

Keywords: Molecular imaging; magnetic resonance imaging; nuclear imaging; rheumatoid arthritis.

Figure 1

A joint (the place where two bones meet) is surrounded by a capsule that protects and supports it. The joint capsule is lined with a type of tissue called synovium, which produces synovial fluid that lubricates and nourishes joint tissues. In rheumatoid arthritis, the synovium becomes inflamed, causing warmth, redness, swelling, and pain. As the disease progresses, the inflamed synovium invades and damages the cartilage and bone of the joint. Surrounding muscles, ligaments, and tendons become weakened. Rheumatoid arthritis also can cause more generalized bone loss that may lead to osteoporosis (fragile bones that are prone to fracture) (Image courtesy of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (http://www.niams.nih.gov/Health_Info/Rheumatic_Disease/default.asp - last accessed February 2012)).

Figure 2

A 74-year-old woman with 3.5-year history of RA who experienced a recurrence and was being considered for infliximab therapy. (A) Anterior and RAO MIP image obtained using FDG-PET/CT shows typical RA lesions in the large joints. (B and C) Axial PET/CT fusion image of the hip joint in the same patient. The large arrows indicate synovitis in the acetabulum and femoral head. The small arrows indicate enthesopathies at the ischium and greater trochanter (D) Bone scan of the same patient shows mild changes in the joints. (Reprinted from Kubota K, Ito K, Morooka M, Minamimoto R, Miyata Y, Yamashita H, Takahashi Y and Mimori A. FDG PET for rheumatoid arthritis: basic considerations and whole-body PET/CT. Ann NY Acad Sci 2011; 1228: 29-38; by permission of John Wiley and Sons).

Figure 3

Hybrid ¹⁸F-FDG PET-MRI of the hand in early RA. a axial and coronal display of PET co-registered with b axial and coronal T1-weighted MRI. c True hybrid ¹⁸F-FDG PET-MRI of the hand. (Reprinted with kind permission from Springer Science+Business Media: Miese F, Scherer A, Ostendorf B, Heinzel A, Lanzman RS, Kropil P, Blondin D, Hautzel H, Wittsack HJ, Schneider M, Antoch G, Herzog H and Shah NJ. Hybrid ¹⁸F-FDG PET-MRI of the hand in rheumatoid arthritis: initial results. Clin Rheumatol 2011; 30: 1247-1250, Figure 1).

Figure 4

Images obtained 4 h after injection of ^99mTc-1.2B6-Fab (left) and ^99mTc-HDP (right) in two patients with RA. The images on the top correlate well; the bottom images show discordance between the lack of uptake of the mAb fragment and diffuse bony uptake. (Reprinted from Jamar F, Houssiau FA, Devogelaer JP, Chapman PT, Haskard DO, Beaujean V, Beckers C, Manicourt DH and Peters AM. Scintigraphy using a technetium-99m labelled anti-E-selectin Fab fragment in rheumatoid arthritis. Rheumatology (Oxford) 2002; 41: 53-61; by permission of Oxford University Press).

Figure 5

Scintigraphy with ^99mTc-anti-CD3 of the knees shows an increase in the uptake of these areas in late images. Images taken (A) 1 h and (B) 3 h after endovenous injection of the radiopharmaceutical. (Reprinted from Lopes FP, de Azevedo MN, Marchiori E, da Fonseca LM, de Souza SA and Gutfilen B. Use of ^99mTc-anti-CD3 scintigraphy in the differential diagnosis of rheumatic diseases. Rheumatology (Oxford) 2010; 49: 933-939; by permission of Oxford University Press).

Figure 6

(A) Right hand with fourth PIP joint swelling and capsular bulging. (B) Hand scintigraphy scan, showing increase in uptake of ^99mTc-anti-TNF-a in the fourth right (PIP) (arrow), third and fourth left PIP and wrists. (C and D) Right-hand MRI coronal (C) and axial (D) slices showing fourth PIP synovitis. (Reprinted from Roimicher L, Lopes FP, de Souza SA, Mendes LF, Domingues RC, da Fonseca LM and Gutfilen B. ^99mTc-anti-TNF-α scintigraphy in RA: a comparison pilot study with MRI and clinical examination. Rheumatology (Oxford) 2011; 50: 2044-2050; by permission of Oxford University Press).

Figure 7

Tenosynovitis. (A) T2-weighted fat-suppressed axial image shows high signal surrounding the flexor tendons (arrows), which represents fluid or edema. (B) T1-weighted axial image shows intermediate signal surrounding the flexor tendons (arrows). (C) T1-weighted fat-suppressed axial image after Gadolinium contrast administration shows high signal enhancement (arrows), representing tenosynovitis surrounding the flexor tendons (Image courtesy of Dr. Kathleen Brindle, the George Washington University, Washington D.C.).

Figure 8

Synovitis/synovial hypertrophy. (A) T1-weighted fat-suppressed axial image shows intermediatesignal of the synovium surrounding the metacarpalbases. (B) T1-weighted fat-suppressed axialimage after Gadolinium contrast administrationshows high signal enhancing synovium (arrows)around the base of the fourth metacarpal. The findingssuggest synovitis or synovial hypertrophy (Imagecourtesy of Dr. Kathleen Brindle, the George WashingtonUniversity, Washington D.C.).

Figure 9

(A) Bone edema. T2-weighted fat-suppressed coronal image shows intermediate signal in the bone of the second metacarpal (arrow) and in the carpal bones (arrowheads). In the setting of RA this can represent edema. (B) T1-weighted fat-suppressed axial image shows uniform intermediate signal through the metacarpal bases. T1-weighted images without contrast are not sensitive for detection of bone edema. (C) T1-weighted fat-suppressed axial image after Gadolinium contrast enhancement shows diffusely increased bone signal at the base of the second metacarpal (arrow), consistent with enhancing edema (Image courtesy of Dr. Kathleen Brindle, the George Washington University, Washington D.C.).

Figure 10

Erosions. T1-weighted coronal image shows erosive changes of the navicular, multangular, and first metacarpal (arrows) (Image courtesy of Dr. Kathleen Brindle, the George Washington University, Washington D.C.).