Residency · Residency · Nuclear Medicine
PET/CT in Infection and Inflammation
Overview
FDG accumulates in activated macrophages, neutrophils, and lymphocytes because these cells upregulate GLUT transporters and hexokinase activity during the inflammatory response. Non-oncologic applications of FDG PET/CT are expanding in the fields of infection and inflammatory disease. While FDG PET/CT offers high sensitivity for detecting inflammatory foci, its specificity is variable, and clinical context is essential for accurate interpretation.
Fever of Unknown Origin (FUO)
Definition and Role
Fever of unknown origin is defined as a temperature exceeding 38.3 degrees Celsius on multiple occasions, lasting more than 3 weeks, with no diagnosis established after 1 week of investigation. FDG PET/CT identifies a cause in 40 to 70% of FUO cases, detecting occult infections, malignancies, and inflammatory conditions. It is superior to conventional workup with CT and gallium scanning for localizing the source of fever.
Diagnostic Yield by Etiology
The spectrum of diagnoses identified by PET/CT in FUO includes infections (endocarditis, abscesses, osteomyelitis, and infected devices), malignancy (lymphoma being the most common, along with solid tumors), and inflammatory conditions (adult-onset Still disease, vasculitis, sarcoidosis, and polymyalgia rheumatica). A negative PET in the setting of FUO generally predicts a benign clinical course.
<image>FDG PET/CT in a patient with fever of unknown origin revealing an occult psoas abscess as the source of fever, not identified on prior CT imaging</image>
Prosthetic Joint Infection
Hip and Knee Prostheses
FDG PET/CT differentiates septic from aseptic loosening of prosthetic joints based on the pattern of periprosthetic FDG uptake. Aseptic loosening produces mild, diffuse uptake along the bone-prosthesis interface, while infection produces intense, focal uptake at the bone-prosthesis interface, especially at the middle third of the prosthesis. Sensitivity ranges from 85 to 95% and specificity from 80 to 90% for periprosthetic infection. PET/CT is more accurate than the bone scan and white blood cell scan combination for hip prostheses.
Limitations
Normal post-operative uptake can persist for 1 to 2 years after uncomplicated arthroplasty, potentially confusing interpretation. Metal artifact from the prosthesis on the CT component can degrade image quality. Dual-time-point imaging, where increasing SUV over time suggests infection, may improve specificity.
Vascular Graft Infection
Aortic Graft Infection
Aortic graft infection is a life-threatening complication with mortality ranging from 25 to 75%. FDG PET/CT achieves a sensitivity of approximately 95% and specificity of 80 to 90%. The key interpretive challenge is distinguishing normal post-surgical healing (diffuse, low-grade uptake persisting up to 4 to 6 weeks) from true infection (focal, intense uptake, especially when associated with gas or fluid collections on CT). FDG uptake is graded relative to the liver, with activity exceeding liver uptake suggesting infection.
Interpretation Caveats
Low-grade uptake around Dacron grafts can persist indefinitely due to a foreign body reaction, while PTFE grafts show less chronic inflammatory response. Focal, intense uptake with corresponding CT findings such as perigraft fluid and air is the most specific pattern for infection.
<image>FDG PET/CT showing focal intense uptake around an infected aortic graft with perigraft fluid on the CT component, consistent with graft infection</image>
Sarcoidosis
Disease Activity Assessment
FDG PET/CT evaluates the extent and activity of sarcoidosis by demonstrating active granulomatous inflammation in lymph nodes, lungs, liver, spleen, bone, and skin. The lambda sign, consisting of bilateral hilar and right paratracheal nodal uptake, is characteristic though not pathognomonic. The panda sign shows symmetric parotid and lacrimal gland uptake.
Clinical Applications
PET/CT identifies occult sites of disease suitable for biopsy (especially extrapulmonary sites), monitors treatment response to corticosteroids or steroid-sparing agents, assesses cardiac sarcoidosis, and evaluates disease activity when serum ACE levels and other markers are inconclusive.
Cardiac Sarcoidosis
The cardiac sarcoidosis protocol requires prolonged fasting for more than 12 to 18 hours or a high-fat, low-carbohydrate diet for 24 to 48 hours to suppress physiologic myocardial glucose uptake. Some protocols add intravenous heparin before FDG injection to shift myocardial metabolism toward free fatty acids. Focal or focal-on-diffuse FDG uptake in the myocardium indicates active inflammation. Resting perfusion defects with corresponding FDG uptake suggest active inflammation in areas of early fibrosis. Perfusion defects without FDG uptake indicate completed fibrosis or scarring.
<image>Cardiac sarcoidosis on FDG PET/CT (with dietary suppression protocol) showing focal intense myocardial FDG uptake in the basal septum and lateral wall with corresponding perfusion defects on rest perfusion imaging</image>
Large Vessel Vasculitis
Giant Cell Arteritis (GCA) and Takayasu Arteritis
FDG PET/CT detects large vessel inflammation before structural changes occur on conventional imaging. The characteristic pattern is smooth, linear FDG uptake along the aorta and its major branches. Vascular uptake is graded relative to the liver on a 0 to 3 scale: grade 0 indicates no uptake, grade 1 is less than liver, grade 2 is equal to liver, and grade 3 is greater than liver and is highly suggestive of vasculitis. Sensitivity for active large vessel vasculitis is approximately 80 to 90%.
Limitations
Corticosteroid therapy rapidly reduces FDG uptake, so scanning should be performed before or within 3 days of starting steroids. Atherosclerosis causes patchy, irregular vascular uptake that must be distinguished from the smooth, continuous pattern of vasculitis. PET/CT cannot reliably assess temporal arteries or intracranial vessels because of their small size and adjacent brain uptake.
Infective Endocarditis
Role of PET/CT
FDG PET/CT has been added to the modified Duke criteria as a major criterion in the 2023 ESC guidelines. It detects perivalvular abscesses, mycotic aneurysms, and septic emboli. It is particularly useful for prosthetic valve endocarditis, where sensitivity ranges from 75 to 95%. Sensitivity for native valve endocarditis is lower, at approximately 30 to 40%. Scanning should be performed after at least 1 week of antibiotic therapy to reduce false negatives from pre-treatment inflammation.
Technical Considerations
Cardiac-gated acquisition improves detection of small perivalvular abscesses. Prolonged fasting or a high-fat, low-carbohydrate diet is required to suppress myocardial uptake, similar to the cardiac sarcoidosis protocol. Findings should be correlated with echocardiography (TTE and TEE) and clinical findings.
Osteomyelitis
Diabetic Foot Osteomyelitis
FDG PET/CT has sensitivity of approximately 80 to 90% and specificity of 75 to 85% for diabetic foot osteomyelitis. Active Charcot neuroarthropathy also shows increased FDG uptake, which can limit specificity. White blood cell-labeled scans (In-111 or Tc-99m HMPAO) may be more specific in the complicated diabetic foot. FDG PET/CT is useful for vertebral osteomyelitis and discitis.
Vertebral Osteomyelitis
FDG PET/CT is highly sensitive for spinal infection. It distinguishes degenerative changes (mild uptake at endplates) from infection (intense uptake with disc involvement). It also monitors treatment response, with declining FDG uptake correlating with clinical improvement.
<image>FDG PET/CT in vertebral osteomyelitis/discitis showing intense uptake at the L3-L4 disc space and adjacent vertebral bodies with associated epidural phlegmon on CT</image>
| Clinical Indication | Sensitivity | Specificity | Key Consideration |
|---|---|---|---|
| Fever of unknown origin | Identifies cause in 40–70% | Variable | Negative PET predicts benign course |
| Prosthetic joint infection | 85–95% | 80–90% | Normal uptake persists 1–2 years post-op |
| Aortic graft infection | ~95% | 80–90% | Dacron grafts show chronic low-grade uptake |
| Large vessel vasculitis | 80–90% | High | Scan before steroids; smooth linear pattern |
| Prosthetic valve endocarditis | 75–95% | High | Requires myocardial suppression protocol |
| Native valve endocarditis | 30–40% | High | Limited sensitivity |
| Cardiac sarcoidosis | High | High | Requires 12–18 h fast or high-fat diet |
| Vertebral osteomyelitis | High | Good | Distinguishes from degenerative changes |
| Diabetic foot osteomyelitis | 80–90% | 75–85% | Charcot neuroarthropathy limits specificity |
Clinical Pearls
For cardiac sarcoidosis and endocarditis, patient preparation with dietary suppression of myocardial glucose uptake is critical. Failed suppression renders the study non-diagnostic.
A negative FDG PET/CT in fever of unknown origin is reassuring and generally predicts spontaneous resolution.
Vascular graft uptake must be interpreted with knowledge of graft material, time since surgery, and CT findings.
Atherosclerosis causes focal, irregular, patchy vascular uptake, in contrast to the smooth, linear pattern characteristic of vasculitis.
In sarcoidosis, PET/CT is more sensitive than serum ACE for detecting active disease and monitoring treatment response.
Post-operative inflammatory changes can persist for weeks to months, and the timing of the scan relative to surgery is crucial for accurate interpretation.
References
- Defined Role of FDG PET/CT in Fever of Unknown Origin. Seminars in Nuclear Medicine, 2019.
- Defined Role of FDG PET/CT in Vascular Graft Infection. European Journal of Nuclear Medicine, 2018.
- Defined Role of FDG PET/CT in Cardiac Sarcoidosis. JACC Cardiovascular Imaging, 2017.
- ESC Guidelines on Infective Endocarditis (2023): Role of FDG PET/CT.
- Defined Role of FDG PET/CT in Large Vessel Vasculitis. Annals of Internal Medicine, 2018.
