Abstract
Most commonly infectious processes in children involve the peripheral skeleton, lungs, kidneys, brain, and heart. Pediatric infections are usually of viral and bacterial origins. Fungal etiology can be found, mainly in children with immunodeficiency. Neonates also have immature immunity and are prone to infections with a less favorable prognosis. Conventional techniques used to evaluate infectious and inflammatory processes in children provide high-resolution images but are limited since only insignificant findings are seen in early disease stages and the differential diagnosis with coexisting pathologies and/or post-treatment changes is challenging. Nuclear Medicine procedures play an important role in diagnosing and monitoring pediatric infections, and inflammatory and granulomatous diseases. Several SPECT radiotracers used in the past for functional imaging of infection and inflammatory processes, such as 67Gallium citrate and 111In-labelled WBCs are not being used anymore routinely in pediatric patients and only rarely in adults, mainly in centers with limited or no access to 99mTc-labelled leukocytes (WBCs) and PET imaging. The value of Nuclear Medicine tests has increased with the implementation of hybrid SPECT/CT, PET/CT, and PET/MRI imaging.
You have full access to this open access chapter, Download chapter PDF
Similar content being viewed by others
Keywords
11.1 Clinical Indications
Commonly evaluated pediatric infectious processes [1,2,3]:
-
Musculoskeletal (MSK) infections
-
Osteomyelitis (diagnosis, differential diagnosis, single vs. multifocal disease)
-
Discitis
-
Arthritis
-
-
Fever of unknown origin (FUO) is at present evaluated with FDG imaging as a second-line diagnostic investigations. The test has high overall performance, mainly in:
Additional indications in children [8]
-
Fungal infections (e.g., aspergillosis and candidiasis).
-
Inflammatory bowel disease (IBD) (diagnosis, extent of disease, differential diagnosis of active disease vs. fibrosis, treatment evaluation) [9].
-
Inflammatory processes
-
Vasculitis
-
Chronic granulomatous diseases (e.g., sarcoidosis)
-
11.2 Pre-exam Information
-
Relevant clinical data:
-
Measure and record the patient height and weight.
-
Current symptoms, pertinent physical findings, duration of signs and symptoms.
-
Pre-existing conditions.
-
Previously or currently received therapy such as antibiotics, corticosteroids, chemotherapy, radiation therapy, and diphosphonates.
-
Prior orthopedic or non-orthopedic surgery, presence of orthopedic hardware.
-
-
Relevant recent imaging studies.
For the activity of all radiotracers to be administered:
Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.
Reference to national regulation guidelines, if available, should be considered.
Study Protocol for Bone Scintigraphy [2, 10]
Patient preparation:
-
Good hydration, patients are instructed to drink at least 2 cups after radiotracer injection, before returning for delayed imaging.
-
Infants should be fed prior or immediately after injection.
-
Children should be encouraged to urinate frequently to reduce the exposure of the bladder.
Radiopharmaceutical, activity, mode of delivery
Radiopharmaceuticals:
-
[99mTc]-MDP (MDP)
Activity:
-
9.3 MBq/kg (0.25 mCi/Kg), minimum dose 40 MBq (1.1 mCi).
Acquisition protocol (Figs. 11.1, 11.2, and 11.3)
-
Position: Supine, with the child comfortably secured to the bed, including feet secured with an inward tilt (allows adequate visualization of the fibulae).
-
Collimators: High or ultra-high low-energy collimator. Pinhole collimator, if available, can improve detection of lesions in the hip joint.
-
Blood flow images: 2–5 s/frame for a total of 60 s, matrix 128 × 128, size appropriate zoom.
-
Early blood pool images: torso 300 Kcounts, extremities 150–200 Kcounts.
-
Late skeletal phase images are typically acquired 3 h after injection.
-
Whole body sweeps: with bed speed adjusted to the child’s age [11].
-
8 cm/min for children aged 4–8 years.
-
10 cm/min for ages 8–12 years
-
12 cm/min for ages 12–16 years
-
15 cm/min over 16 years of age.
-
Multiple spot views (alternatively) to cover the entire skeleton in anterior and posterior projections: matrix 256 × 256, counts: torso 500 Kcounts, skull 300 Kcounts, knees 100–200 Kcounts, hands and feet 50–100 Kcounts. 2nd variant: the time to obtain 500 Kcounts for the torso should be recorded and used to time the acquisition of the other body parts.
-
-
SPECT: 15–30 s/frame, 120 projections, matrix 128 × 128.
-
SPECT/CT (when clinically indicated, if available):
-
CT component using pediatric settings with dose modulation.
-
CT field of view to the finding on SPECT, tube setting depending on whether the CT is intended to be acquired as low dose or fully diagnostic CT (range: between 80 and 110 kVp); CT slice thickness 2–2.5 mm with overlapping cuts.
-
11.3 Study Interpretation of Bone Scintigraphy [12]
-
Osteomyelitis is based on increased local blood flow and bone turnover. The scintigraphic pattern is characterized by increased blood flow and blood pool (tissue hyperemia) and focal increased uptake in the skeletal phase (Fig. 11.1).
-
Osteomyelitis involves mainly the metaphyseal portion of long bones or the metaphyseal equivalents of irregular bones.
-
Less commonly, osteomyelitis presents as diffuse uptake along a segment of a long bone (probably due to periosteal irritation).
-
Mandatory whole-body imaging allows the detection of at times unsuspected multifocal disease including sites related to referred pain. Multifocal osteomyelitis is more common in young infants.
-
Bone scans can differentiate osteomyelitis from soft tissue infections.
-
Cellulitis presents with diffuse increased blood flow and blood pool in soft tissue adjacent to bony structures and mild diffuse increased tracer activity in the same area on the skeletal phase.
-
Arthritis presents with diffuse uptake in all bony structures of a joint, with or without accompanying findings in the blood flow and blood pool phases.
-
Discitis typically presents as increased uptake in two adjacent vertebral bodies above and below the inflamed disc.
-
-
In most cases, an abnormal bone scan can be seen as early as 24 h from the onset of symptoms.
-
Cases with long-standing osteomyelitis show increased blood pool activity surrounding photopenic defects (Fig. 11.2). On the delayed images, there are corresponding cold lesions in keeping with bony abscesses. The differential diagnosis includes infarcted bone.
-
Antibiotic therapy does not affect bone scan findings of osteomyelitis in the short run.
Study Protocol for Tc-WBC Scan [8, 13]
Patient preparation:
-
Patients do not need to fast and may take all their usual medications.
-
The patient should be well hydrated.
-
Explain to patients and parents/caregivers that the procedure is long and requires withdrawal of relatively large amounts of blood (considering the specific pediatric population).
Radiopharmaceutical, activity, mode of delivery
Radiopharmaceutical
-
[99mTc]-WBC
Activity
-
3.7–7.4 MBq/kg (0.1–0.2 mCi/Kg), minimum dose 40 MBq (1.1 mCi)
For detailed instructions regarding the WBC labelling technique, see appropriate guidelines. The blood volume required for WBC labelling has to be adjusted and reduced as much as possible in young infants [14].
Acquisition protocol (Fig 11.4)
-
Collimator: low energy, high resolution, parallel hole.
-
Scanning field: related to clinical indication should be either whole body or limited FOV to area of clinical complaints.
-
Acquisition protocol:
-
Early images, 30 min post-injection, including of the chest and upper abdomen as well as images for in vivo quality control of WBC labelling.
-
Delayed images: 3–4 h post-injection.
-
Late images: 20–24 h post-injection.
-
-
Acquisition parameters—static images:
-
Size appropriate zoom, matrix 256 × 256.
-
Acquisition options:
-
Time corrected for isotope decay: early images are acquired with a set number of counts or time, followed by delayed and late images corrected for the 99mTc 6-h half-life. Different images can be compared with the same intensity scale avoiding operator-dependent changes in the image display.
-
Fixed time/image: 5–10 min/projection. Difficult to interpret because of interfering data from other organs.
-
-
-
SPECT or SPECT/CT (recommended if available): Usually performed after the delayed step (3–4 h post-injection).
-
SPECT parameters if performed after delayed step: 20–30 sec/step (depending on the injected activity).
-
SPECT can be also added to the late step (20–24 h post-injection) with following parameters:
-
30–50 sec/step (depending on the injected activity and FOV to be imaged, longer for peripheral parts, shorter for abdomen).
-
Indicated if there are new sites of pathological uptake not seen on earlier scans.
-
-
-
Modified parameters for IBD: Images acquisition at 30 min and 2–3 h post-injection only (Fig. 11.5).
11.4 Study Interpretation of Tc-WBC Scan [13]
Diagnosis of infection is made by comparing delayed and late images:
-
Negative: no uptake or clear decrease of intensity of uptake between delayed and late images.
-
Positive: clear increase in intensity and/or size of uptake over time in lesion (Fig 11.4).
-
Equivocal, cases such as:
-
Similar/slightly decreasing uptake over time.
-
Slight increase in size and/or intensity over time.
-
Physiologic biodistribution, pitfalls, and positivity criteria:
-
WBCs show a transitory migration to the lungs, followed by accumulation in the spleen and less in the liver and bone marrow.
-
Lung uptake early post-injection is physiologic, but at 4 and 24 h, it is abnormal.
-
Normal bowel activity is seen in 20–30% of children at 1 h due to Tc-HMPAO excretion from the liver.
-
Tc-WBCs migrate from spleen and bone marrow to infected tissues. Therefore, in cases with infection there is an increase in uptake over time in sites of disease while bone marrow and spleen activity decrease.
-
The rate of Tc-WBC accumulation in infection depends on:
-
Location: earlier in cardio-vascular vs. bone and CNS infection.
-
Virulence: higher in active vs. chronic processes.
-
Pathogen: lower in fungal vs. bacterial infection.
-
Antibiotic or steroid therapy may decrease Tc-WBC uptake.
-
Study Protocol for [18F] -FDG [2, 6, 15, 16]
Patient preparation:
-
Fast: 4 h before tracer injection and during the uptake phase is recommended in adults and adolescents. This duration should be shortened according to age in young children, toddlers, and infants.
-
Good hydration with plain, unflavored water.
-
Serum glucose level must be measured before radiotracer administration and should be below 200 mg/dL (11.1 mmol/L), preferably below 140 mg/dL (7.8 mmol/L) [17].
Radiopharmaceutical, activity, mode of delivery
Radiopharmaceuticals:
-
[18F] -FDG (FDG)
Activity
-
3.7–5.2 MBq/kg (0.1–0.14 mCi/kg) minimum 26 MBq (0.7 mCi).
Acquisition protocol
-
Uptake time: 45–60 min.
-
Scanning field: related to clinical indication should be either vertex-to-feet or limited FOV to area of clinical complaints.
-
Acquisition protocol: 2–4 min/bed position - these parameters will potentially change with the implementation of new PET technology (see also Chap. 10).
11.5 Study Interpretation of FDG
-
Positivity criteria: focal or non-focal abnormal tracer uptake.
-
False negatives: Lesion located adjacent to and masked by physiologic tracer activity.
11.6 Correlative Imaging [18]
-
Plain radiographs are readily available and are associated with a low radiation burden. They are used in children with suspected pulmonary and MSK infections. In patients with a skeletal pathology, this test is used mainly for excluding fractures and bone tumors in the differential diagnosis of suspected osteomyelitis.
-
US is primarily used to investigate soft tissue infections and inflammatory processes.
-
CT is readily available at present. Radiation exposure can be reduced by employing specialized pediatric protocols. As a component of SPECT/CT and PET/CT, it can increase the specificity and accuracy of nuclear medicine tests.
-
MRI advantages stem from its lack of ionizing radiation. It also has higher soft tissue contrast than CT.
11.7 Red Flags [2]
Tc-MDP
-
Cannot distinguish between infectious and non-infectious arthritis.
-
Cannot differentiate between infection and malignancies, such as osteosarcoma.
-
Cannot detect extension of spinal infection from the disc to the adjacent soft tissues. These findings are best evaluated with MRI.
-
In cases of discitis, there may be a lag of one week between the onset of symptoms and the first appearance on the bone scan.
-
A negative bone scan in the presence of persistent fever does not exclude the diagnosis of arthritis and may reflect pyomyositis and needs to be further assessed.
WBC
-
Children with severe neutropenia may lack sufficient leukocytes for adequate WBC labelling.
-
The large quantity of blood needed for the procedure is limiting its use in neonates and young children.
-
The study has lower performance indices in chronic infections and acute spinal infections.
-
Visualization of liver and bowel on later images can produce false positive images in patients with suspected IBD.
FDG
-
Radiotracer uptake is not specific to infection.
-
Cannot differentiate between infection and (sterile) inflammation.
-
Cannot differentiate between infection and malignancy.
Matching of Radiotracers Used for Specific Pediatric Infectious and Inflammatory Processes
11.8 Take Home Messages
-
Knowledge regarding the pre-test probability of infection is essential:
-
In low pre-test probability of infection and suspected chronic or non-bacterial processes, FDG imaging is preferred.
-
In case of high WBC counts, ESR or CRP values: Tc-WBC scan can be the first test.
-
WBC accumulation is generally more specific for infection than increased FDG uptake.
-
-
For WBC studies:
-
Images from different time points have to be displayed at the same intensity scale (Figs. 11.4 and 11.5).
-
Any adjustment of the image intensity scale must be applied to all images together to avoid operator bias.
-
Patients receiving antibiotic treatment should not be excluded from performing Tc-WBC scans.
-
-
For FDG imaging:
MSK infection [21]:
-
Three-phase bone scintigraphy, highly sensitive for diagnosing osteomyelitis in uncomplicated bones is suboptimal in patients with pre-existing fracture or orthopedic hardware. Bone scintigraphy in non-oncological indications is further discussed in detail in Chap. 10.
-
Hybrid imaging is associated with a significant improvement in specificity (Figs. 11.3 and 11.6). The SPECT/PET component detects the presence of an active process while on the CT component characteristic findings include areas of cortical destruction and adjacent soft tissue abscess or empyema.
-
Labelled WBC has been reported in only limited studies/cases of MSK infection in children. If at all, in cases of MSK pathologies this test usually follows bone scintigraphy.
-
FDG imaging shows high-performance indices even in challenging settings such as [22]:
-
Chronic and/or low-grade MSK infection (Fig 11.6).
-
In the axial skeleton, including cases with suspected spinal fusion hardware infection (superior to WBC).
-
FDG imaging can also detects extraosseous lesions.
-
-
In children with FUO, the performance indices are similar to those reported in adults.
-
Has a higher positive yield in children with fever early during the disease (less than 3 months), and in those with abnormal laboratory investigations (leukocytosis, neutrophilia, high CRP, ESR) (Figs. 11.6, 11.7, 11.8, and 11.9).
-
Can identify organs or tissues likely to contain the source of fever, thus guiding further tests including tissue sampling procedures.
-
Has a high NPV and it is thus unlikely to find a focal etiology of FUO in cases with a negative study.
11.9 Representative Case Examples
Case 11.1 Osteomyelitis, Tc-MDP (Fig. 11.1)
Case 11.2 Osteomyelitis, Tc-MDP (Fig. 11.2)
Case 11.3 Osteomyelitis in Complicated Bone, Tc-MDP (Fig. 11.3)
Case 11.4 Infected Hematoma of the Skull, Tc-WBC (Fig. 11.4)
Case 11.5 Inflammatory Bowel Disease, Tc-WBC (Fig. 11.5)
Case 11.6 Chronic Recurrent Multifocal Osteomyelitis, FDG (Fig. 11.6)
Case 11.7 Fever of Unknown Origin (FUO), Aspergillosis, FDG (Fig. 11.7)
Case 11.8 FUO, Septic Emboli, FDG (Fig. 11.8)
Case 11.9 FUO, Pericarditis, FDG (Fig. 11.9)
Case 11.10 Vasculitis, FDG—PET/MRI (Fig. 11.10)
References
Signore A, et al. Nuclear medicine imaging in pediatric infection or chronic inflammatory diseases. Semin Nucl Med. 2017;47(3):286–303.
Parisi MT, et al. Radionuclide imaging of infection and inflammation in children: a review. Semin Nucl Med. 2018;48(2):148–65.
Ropers FG, et al. Evaluation of FDG-PET/CT use in children with suspected infection or inflammation. Diagnostics (Basel). 2020;10(9):715.
Sturm E, et al. Fluordeoxyglucose positron emission tomography contributes to management of pediatric liver transplantation candidates with fever of unknown origin. Liver Transpl. 2006;12(11):1698–704.
Wang SS, et al. The clinical utility of fluorodeoxyglucose-positron emission tomography for investigation of fever in immunocompromised children. J Paediatr Child Health. 2018;54(5):487–92.
Pijl JP, et al. Role of FDG-PET/CT in children with fever of unknown origin. Eur J Nucl Med Mol Imaging. 2020;47(6):1596–604.
Chang L, et al. Search of unknown fever focus using PET in critically ill children with complicated underlying diseases. Pediatr Crit Care Med. 2016;17(2):e58–65.
Signore A, et al. Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline. Eur J Nucl Med Mol Imaging. 2018;45(10):1816–31.
Charron M. Pediatric inflammatory bowel disease imaged with Tc-99m white blood cells. Clin Nucl Med. 2000;25(9):708–15.
Drubach LA. Nuclear medicine techniques in pediatric bone imaging. Semin Nucl Med. 2017;47(3):190–203.
Van den Wyngaert T, et al. The EANM practice guidelines for bone scintigraphy. Eur J Nucl Med Mol Imaging. 2016;43(9):1723–38.
Palestro CJ. Infection and inflammation. In: Treves ST, editor. Pediatric nuclear medicine and molecular imaging. New York: Springer; 2014. p. 541–69.
Aydın F, Kın Cengiz A, Güngör F. Tc-99m labeled HMPAO white blood cell scintigraphy in pediatric patients. Mol Imaging Radionucl Ther. 2012;21(1):13–8.
de Vries EF, et al. Guidelines for the labelling of leucocytes with (99m)Tc-HMPAO. Inflammation/Infection Task group of the European Association of Nuclear Medicine. Eur J Nucl Med Mol Imaging. 2010;37(4):842–8.
Servaes S. Imaging infection and inflammation in children with (18)F-FDG PET and (18)F-FDG PET/CT. J Nucl Med Technol. 2011;39(3):179–82.
Houseni M, et al. Applications of PET/CT in pediatric patients with fever of Unknown Origin. PET Clin. 2008;3(4):605–19.
Vali R, et al. SNMMI Procedure Standard/EANM Practice Guideline on Pediatric (18)F-FDG PET/CT for Oncology 1.0. J Nucl Med. 2021;62(1):99–110.
Dhar AV, et al. Team Approach: Pediatric Musculoskeletal Infection. JBJS Rev. 2020;8(3):e0121.
Rabkin Z, Israel O, Keidar Z. Do hyperglycemia and diabetes affect the incidence of false-negative 18F-FDG PET/CT studies in patients evaluated for infection or inflammation and cancer? A Comparative analysis. J Nucl Med. 2010;51(7):1015–20.
Kagna O, et al. Does Antibiotic Treatment Affect the Diagnostic Accuracy of (18)F-FDG PET/CT Studies in Patients with Suspected Infectious Processes? J Nucl Med. 2017;58(11):1827–30.
Bagrosky BM, et al. 18F-FDG PET/CT evaluation of children and young adults with suspected spinal fusion hardware infection. Pediatr Radiol. 2013;43(8):991–1000.
Warmann SW, et al. Follow-up of acute osteomyelitis in children: the possible role of PET/CT in selected cases. J Pediatr Surg. 2011;46(8):1550–6.
Jasper N, et al. Diagnostic value of [(18)F]-FDG PET/CT in children with fever of unknown origin or unexplained signs of inflammation. Eur J Nucl Med Mol Imaging. 2010;37(1):136–45.
del Rosal T, et al. 18F-FDG PET/CT in the diagnosis of occult bacterial infections in children. Eur J Pediatr. 2013;172(8):1111–5.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
The opinions expressed in this chapter are those of the author(s) and do not necessarily reflect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent
Open Access This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http://creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.
Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.
The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Copyright information
© 2023 The Author(s)
About this chapter
Cite this chapter
Israel, O., Estrada-Lobato, E., Pascual, T.N. (2023). Infection and Inflammation Imaging. In: Bar-Sever, Z., Giammarile, F., Israel, O., Nadel, H. (eds) A Practical Guide for Pediatric Nuclear Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-67631-8_11
Download citation
DOI: https://doi.org/10.1007/978-3-662-67631-8_11
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-67630-1
Online ISBN: 978-3-662-67631-8
eBook Packages: MedicineMedicine (R0)