Functional Imaging of Inflammatory Diseases Using Nuclear Medicine Techniques  Sandip Basu, MBBS (Hons), DRM, DNB, MNAMS, Hongming Zhuang, MD, PhD, Drew A. Torigian, MD, MA, Joshua Rosenbaum, BA, Wengen Chen, MD, PhD, Abass Alavi, MD, PhD (Hon), DSc (Hon)  Seminars in Nuclear Medicine  Volume 39, Issue 2, Pages 124-145 (March 2009) DOI: 10.1053/j.semnuclmed.2008.10.006 Copyright © 2009 Terms and Conditions

Figure 1 Classic λ (lambda) sign in the chest attributable to mediastinal and hilar lymphadenopathy as demonstrated by planar 67Ga whole-body scintigraphy. Note that the spleen is significantly enlarged and is likely affected by the disease. (Reproduced with permission from Yu et al.12) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 2 This 43-year-old woman with newly diagnosed invasive ductal right breast cancer underwent a FDG-PET examination for preoperative staging. The PET study revealed multiple sites of increased uptake in bilateral hilar and mediastinal regions consistent with an FDG avid metabolically active process; the pattern of activity is not typical for breast cancer metastases and can be caused by conditions like lymphoma or sarcoidosis. Histopathologic examination of these lesions obtained by mediastinoscopy demonstrated noncaseating granulomas without malignant cells noted due to sarcoidosis. (Reproduced with permission from Yu et al.12) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 3 Patient A: Coronal images show a typical pattern of FDG uptake in a patient with sarcoidosis. Increased uptake is noted in the lymph nodes in the supraclavicular, mediastinal, and hilar regions bilaterally. Patient B: Multiplanar images show lymph nodes in hilar and mediastinal locations in another patient with sarcoidosis. (Reproduced with permission from Yu et al.12) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 4 Monitoring response to treatment with FDG-PET in sarcoidosis. The pretherapy scan (top row) show significant disease activity in the mediastinum, whereas the posttherapy scan (bottom row) demonstrates marked improvement with significantly decreased metabolic activity at sites of lymphadenopathy. (Reproduced with permission from Yu et al.12) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 5 This 70-year-old man has a history of spiculated right upper lobe lung nodule and hilar lymphadenopathy. An FDG-PET/CT demonstrates increased FDG uptake in the nodule (A, CT in lung windows) and in the lymph nodes (B, CT in mediastinal windows), consistent with a metabolically active process (red/white color focus). A core biopsy was obtained and showed nonnecrotizing granulomas. AC, attenuation corrected. (Reproduced with permission from Yu et al.12) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 6 FDG-PET/CT scan of a 69 year-old man with lung cancer. Images include CT on the left, PET in the middle, and fused PET/CT on the right. There is intense uptake of FDG in the wall of the descending thoracic aorta, often noted in patients with atherosclerosis. Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 7 In this 77-year-old woman, (A) 67Ga-citrate scan shows no abnormal findings, whereas (B) MIP image of FDG-PET and (C) FDG-PET/CT fused image demonstrate intense FDG uptake in the walls of the thoracic and abdominal aorta, and in carotid, subclavian and iliac arteries due to large-vessel vasculitis. (Reproduced from Otsuka et al61 with permission from The Journal of Medical Investigation.) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 8 In this 72-year-old woman, the initial FDG-PET image (A) established the diagnosis of vasculitis by demonstrating intense uptake in the aorta and the subclavian arteries while a follow-up PET image after steroid therapy (B) revealed complete disappearance of the abnormalities noted on the initial scan. (Reproduced from Otsuka et al61 with permission from The Journal of Medical Investigation.) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 9 FDG-PET/CT images show significant uptake in the distal ileum which extends to the cecal region which is mildly active (long arrow), clearly demonstrating the high sensitivity of this technique for detection of regional inflammation. Interestingly, there is a serendipitous finding of FDG-avid right lower lobe bronchopneumonia (short arrow), which became symptomatic the day after the PET/CT study was acquired (Reproduced with permission from Basu et al.86) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 10 Shown are sagittal slices through the foot from lateral (left) through medial (right) displayed with (A) FDG-PET, (B) fused PET/CT, (C) CT, and (D) an anatomical reference (Ti, Tibia; Ta, Talus; Ca, calcaneus; na os, naviculare; Cu, cuboid; Cm os, cuneiform mediale; Ci os, cuneiform intermediale; Mt os, metatarsale) in a patient with rheumatoid arthritis. The images demonstrate intense inflammation at the talonavicular and the calcaneotalar joints. Areas with lower intensity are visualized in the talocalcaneal, naviculo-cuneiform, and metatarsophalangeal joints. The ankle joint does not show active inflammation, indicating successful previous synovectomy. Physical examination and conventional radiography in this patient were unable to discriminate which joints in the tarsus region were responsible for this patient's complaints. (Reproduced from Vogel et al106 with kind permission of Springer Science & Business Media.) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 11 FDG-PET images of the knees reveal inflammatory reaction in the joint space (in the intact joint on the left knee but not in the right knee with prosthesis) and surrounding synovial tissue (on both sides), which is commonly noted in patients with osteoarthritis. The role of FDG-PET in the diagnosis and monitoring the course of disease in osteoarthritis is being investigated at this time. Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 12 MRI of the knee (A) demonstrates a benign lesion in the medial femoral condyle, most likely due to an ossifying fibroma or enchondroma (dashed arrow). There is also a tear of the anterior horn of the medial meniscus of the right knee, best appreciated on the sagittal fat suppressed T2 weighted images (solid arrow). FDG-PET (B) shows no FDG uptake in the benign lesion of the right femur. There was, however, an increase in FDG uptake in the medial region of the right knee in an inverted C shaped pattern. After fusion of PET and MRI images (C), the area of curvilinear increased FDG uptake corresponded to the peripheral border of the medial meniscus, suggestive of meniscal tear associated with synovitis. (Reproduced from El-Haddad et al108 with permission from Springer.) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 13 FDG-PET image of the abdomen reveals significant uptake in the right common and external iliac veins with extension to the femoral region due to deep venous thrombosis, which was subsequently confirmed by additional studies. This image clearly demonstrates the potential role of FDG-PET imaging to detect clots in the venous system, which may have implications for assessment of patients with thromboembolic disorders. (Courtesy of Kathryn Morton, MD, University of Utah, Salt Lake City, UT.) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 14 A lower-extremity FDG-PET image of a 48-year-old woman with a history of right calf pain shows an area of intense tracer uptake in the right calf region, consistent with inflammation due to chronic thrombophlebitis. Inflammatory vascular disorders can be detected by FDG-PET, and this case suggests that FDG-PET may assume a role in detecting thrombophlebitis. (Reproduced from Chang et al123 with permission from Lippincott, Williams & Wilkins.) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 15 A 46-year-old man with a 20-year history of Sjögren's syndrome was examined for the recent onset of pain and swelling of the parotid glands, which was more prominent on the right side. Coronal PET images (A) with FDG show diffusely and intensely increased uptake in both sides of the neck (arrows), corresponding to the parotid glands, with slightly more prominence on the right. A biopsy of the right gland confirmed non-Hodgkin's lymphoma. His initial PET showed abnormal FDG uptake in the parotid glands. After rituximab therapy, a follow-up PET (B) confirmed a positive response to treatment. FDG-PET may be useful to monitor the therapeutic response of NHL parotid glands associated with Sjögren's syndrome. (Reproduced from Shih et al125 with permission from Lippincott, Williams & Wilkins.) Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions

Figure 16 Coronal whole-body FDG-PET image reveals significant uptake of FDG in the muscles on the right side involving the buttock, psoas muscle, and upper thigh. This finding was interpreted to represent dermatomyositis in this patient. The role of FDG-PET in this entity is being explored and it is expected that this modality may prove to be of value for the diagnosis of this disease as well as monitoring of response to treatment during the course of the disease. Seminars in Nuclear Medicine 2009 39, 124-145DOI: (10.1053/j.semnuclmed.2008.10.006) Copyright © 2009 Terms and Conditions