Biomarkers Paediatrics
The following list has been reviewed and approved by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR).
PAEDIATRIC MUSCULOSKELETAL IMAGING
Paediatric MSK |
Disease |
Biomarker and evidence for use |
Description of imaging technique |
Pathophysiological process informed by MRI biomarker |
Biomarker measured |
Units of measurement |
Suitable for use in clinical trials |
Juvenile idiopathic arthritis (JIA) -synovial inflammation |
CE MRI1-3! |
T1 fs weighted images, pre- and post Gadolinium |
Key measure in grading synovitis |
Inflammation score |
0 - 3 |
Developmental dysplasia of the hip (DDH) |
US4! |
Coronal section through the mid-acetabulum (standard-view) |
Acetabular dysplasia
|
Alpha angle |
Degrees |
|
DDH |
XR5! |
Pelvic XR |
Acetabular dysplasia |
Acetabular Index Sharp’s angle Wiberg’s CE angle FHEI, ATD, ADR |
Degrees or mm |
|
Biomarkers in development |
DDH |
XR5! |
Pelvic XR |
Acetabular dysplasia |
Ogata angle Acetabular roof angle |
|
Coxarthrosis |
XR5! |
Pelvic XR |
Coxarthrosis |
Joint space width |
|
- Damasio MB, Malattia C, Tanturri de HL, et al. MRI of the wrist in juvenile idiopathic arthritis: proposal of a paediatric synovitis score by a consensus of an international working group. Results of a multicentre reliability study. PediatrRadiol 2012;42:1047-55.
- Nusman CM, Ording Muller LS, Hemke R, et al. Current Status of Efforts on Standardizing Magnetic Resonance Imaging of Juvenile Idiopathic Arthritis: Report from the OMERACT MRI in JIA Working Group and Health-e-Child. J Rheumatol 2016;43:239-44.
- Avenarius DFM, Ording Muller LS, Rosendahl K. Joint Fluid, Bone Marrow Edemalike Changes, and Ganglion Cysts in the Pediatric Wrist: Features That May Mimic Pathologic Abnormalities-Follow-Up of a
- Rosendahl K, Aslaksen A, Lie RT, Markestad T. Reliability of ultrasound in the early diagnosis of developmental dysplasia of the hip. PediatrRadiol 1995;25:219-24.
- Engesaeter IO, Laborie LB, Lehmann TG, et al. Radiological findings for hip dysplasia at skeletal maturity. Validation of digital and manual measurement techniques. Skeletal Radiol 2012;41:775-85.
PAEDIATRIC NEURO
Neuro |
Disease |
Biomarker and evidence for use |
Description of imaging technique |
Pathophysiological process informed by MRI biomarker |
Biomarker measured |
Units of measurement |
Suitable for use in clinical trials |
Hydrocephalus |
US1! |
Coronal view through the 3rd ventricle |
Hydrocephalus |
Ventricular / SAS dimensions |
mm |
- Gravendeel J, Rosendahl K. Cerebral biometry at birth and at 4 and 8 months of age. A prospective study using US. Ped Radiol 2010 Oct;40(10):1651-6.
PHYSICAL ABUSE
|
Disease |
Biomarker and evidence for use |
Description of imaging technique |
Pathophysiological process informed by MRI biomarker |
Biomarker measured |
Units of measurement |
Suitable for use in clinical trials
|
Physical abuse |
XR skeletal survey1! |
High-resolution radiographs |
Acute fracture of shafts of tubular bones, clavicles or ribs |
Soft tissue swelling No periosteal reaction or callus2,3! |
Number |
Physical abuse |
XR skeletal survey 1! |
High-resolution radiographs |
Healing fracture of shafts of tubular bones, clavicles or ribs |
Periosteal reaction, callus, or remodelling2,3! |
Number |
|
Physical abuse |
XR skeletal survey1! |
High-resolution radiographs |
Metaphyseal fracture ≤ 2 weeks of age4! |
Thickness4! |
mm (≤1mm) 4 |
|
Physical abuse |
XR skeletal survey1! |
High-resolution radiographs |
Metaphyseal fracture > 2 weeks of age4! |
Thickness4! |
mm (>1mm) 4 |
|
Physical abuse |
CT head1! |
Axial, coronal, sagittal and 3D recons (bone algorithm)1,5! |
Acute skull fracture (≤14 days) |
Overlying scalp swelling |
Presence/absence |
|
Abusive head injury |
CT or MRI1! |
RCR protocol1! |
Intracranial/spinal haemorrhage, hypoxic ischaemic injury6! |
Presence/absence |
Presence/absence |
- The radiological investigation of suspected physical abuse in children RCR 2017
- Walters MM, Forbes PW, Buonomo C, Kleinman PK Healing patterns of clavicular birth injuries as a guide to fracture dating in cases of possible infant abuse Pediatr Radiol 2014;44:1224-1229
- Fadell M, Miller A, Trefan L et al Radiological features of healing in newborn clavicular fractures Eur Radiol 2017;27:2180-2187
- Karmazyn B, Marine MB, Wanner MR et al Establishing signs for acute and healing phases of distal tibial classic metaphyseal lesions Pediatr Radiol 2020;50:715-725
- Choudhary A, Servaes S, Slovis TL et al Consensus statement on abusive head trauma in infants and young children Pediatr Radiol 2018 48:1048-1065
- Martin A, Paddock M, Johns CS et al Avoiding skull radiographs in infants with suspected inflicted injury who also undergo head CT: “A no-brainer” Eur Radiol 2020;30:1480-1487
PAEDIATRIC ONCOLOGY
Paediatric Oncology |
Disease |
Biomarker and evidence for use |
Description of imaging technique |
Pathophysiological process informed by MRI biomarker |
Biomarker measured |
Units of measurement |
Suitable for use in clinical trials |
Neuroblastoma |
ADC1-4! |
Diffusion weighted imaging |
Restriction of the free diffusibility correlates with histologic subtypes |
Diffusion restriction |
mm2/s |
Nephroblastoma |
ADC5-8! |
Diffusion weighted imaging |
Restriction of the free diffusibility correlates with histologic subtypes |
Diffusion restriction |
mm2/s |
|
Hodgkin Lymphoma |
Deauville Score9-11! |
18F-FDG-PET/CT |
18F-FDG Uptake after chemoth. correlates with outcome |
Points |
n.a. |
|
Neuroblastoma |
SIOPEN Score12,13! |
123I-metaiodobenzylguanidine scintigraphy |
Prognostic value of the SIOPEN skeletal score |
Points |
n.a. |
|
Neuroblastoma |
18F-FDG14-20! Uptake |
18F-FDG-PET/CT |
18F-FDG Uptake correlate with tumor grading |
SUV |
n.a. |
|
Brain tumor |
18F-FET Uptake21! |
18F-FET-PET/CT |
Brain tumor detection and recurrence |
SUV |
n.a. |
|
Solid tumor |
Tumor size22-25! RECIST 1.1 |
Cross sectional imaging |
Tumor dimension before and after chemotherapy correlates with outcome |
1 dimensional |
cm |
- Neubauer H, Li M, Müller VR, Pabst T, Beer M. Diagnostic Value of Diffusion-Weighted MRI for Tumor Characterization, Differentiation and Monitoring in Pediatric Patients with Neuroblastic Tumors. Rofo 2017;189:640-50.
- Peschmann AL, Beer M, Ammann B, et al. Quantitative DWI predicts event-free survival in children with neuroblastic tumours: preliminary findings from a retrospective cohort study. Eur Radiol Exp 2019;3:6.
- Serin HI, Gorkem SB, Doganay S, et al. Diffusion weighted imaging in differentiating malignant and benign neuroblastic tumors. Jpn J Radiol 2016;34:620-4.
- Gahr N, Darge K, Hahn G, Kreher BW, von Buiren M, Uhl M. Diffusion-weighted MRI for differentiation of neuroblastoma and ganglioneuroblastoma/ganglioneuroma. Eur J Radiol 2011;79:443-6.
- Hales PW, Olsen Ø E, Sebire NJ, Pritchard-Jones K, Clark CA. A multi-Gaussian model for apparent diffusion coefficient histogram analysis of Wilms’ tumour subtype and response to chemotherapy. NMR Biomed 2015;28:948-57.
- Littooij AS, Nikkels PG, Hulsbergen-van de Kaa CA, van de Ven CP, van den Heuvel-Eibrink MM, Olsen Ø E. Apparent diffusion coefficient as it relates to histopathology findings in post-chemotherapy nephroblastoma: a feasibility study. Pediatr Radiol 2017;47:1608-14.
- Rogers HJ, Verhagen MV, Shelmerdine SC, Clark CA, Hales PW. An alternative approach to contrast-enhanced imaging: diffusion-weighted imaging and T(1)-weighted imaging identifies and quantifies necrosis in Wilms tumour. Eur Radiol 2019;29:4141-9.
- Rogers HJ, Verhagen MV, Clark CA, Hales PW. Comparison of models of diffusion in Wilms’ tumours and normal contralateral renal tissue. Magma 2020.
- Hasenclever D, Kurch L, Mauz-Körholz C, et al. qPET – a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma. Eur J Nucl Med Mol Imaging 2014;41:1301-8.
- Kluge R, Chavdarova L, Hoffmann M, et al. Inter-Reader Reliability of Early FDG-PET/CT Response Assessment Using the Deauville Scale after 2 Cycles of Intensive Chemotherapy (OEPA) in Hodgkin’s Lymphoma. PLoS One 2016;11:e0149072.
- Kurch L, Hasenclever D, Kluge R, et al. Only strongly enhanced residual FDG uptake in early response PET (Deauville 5 or qPET ≥ 2) is prognostic in pediatric Hodgkin lymphoma: Results of the GPOH-HD2002 trial. Pediatr Blood Cancer 2019;66:e27539.
- Morgenstern DA, Pötschger U, Moreno L, et al. Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study. Pediatr Blood Cancer 2018;65:e27363.
- Ladenstein R, Lambert B, Pötschger U, et al. Validation of the mIBG skeletal SIOPEN scoring method in two independent high-risk neuroblastoma populations: the SIOPEN/HR-NBL1 and COG-A3973 trials. Eur J Nucl Med Mol Imaging 2018;45:292-305.
- Kang SY, Rahim MK, Kim YI, et al. Clinical Significance of Pretreatment FDG PET/CT in MIBG-Avid Pediatric Neuroblastoma. Nucl Med Mol Imaging 2017;51:154-60.
- Lee JW, Cho A, Yun M, Lee JD, Lyu CJ, Kang WJ. Prognostic value of pretreatment FDG PET in pediatric neuroblastoma. Eur J Radiol 2015;84:2633-9.
- Li C, Huang S, Guo J, et al. Metabolic Evaluation of MYCN-Amplified Neuroblastoma by 4-[(18)F]FGln PET Imaging. Mol Imaging Biol 2019;21:1117-26.
- Li C, Zhang J, Chen S, et al. Prognostic value of metabolic indices and bone marrow uptake pattern on preoperative 18F-FDG PET/CT in pediatric patients with neuroblastoma. Eur J Nucl Med Mol Imaging 2018;45:306-15.
- Liu CJ, Lu MY, Liu YL, et al. Risk Stratification of Pediatric Patients With Neuroblastoma Using Volumetric Parameters of 18F-FDG and 18F-DOPA PET/CT. Clin Nucl Med 2017;42:e142-e8.
- Melzer HI, Coppenrath E, Schmid I, et al. ¹²³I-MIBG scintigraphy/SPECT versus ¹⁸F-FDG PET in paediatric neuroblastoma. Eur J Nucl Med Mol Imaging 2011;38:1648-58.
- Papathanasiou ND, Gaze MN, Sullivan K, et al. 18F-FDG PET/CT and 123I-metaiodobenzylguanidine imaging in high-risk neuroblastoma: diagnostic comparison and survival analysis. J Nucl Med 2011;52:519-25.
- Dunkl V, Cleff C, Stoffels G, et al. The usefulness of dynamic O-(2-18F-fluoroethyl)-L-tyrosine PET in the clinical evaluation of brain tumors in children and adolescents. J Nucl Med 2015;56:88-92.
- Orr KE, McHugh K. The new international neuroblastoma response criteria. Pediatr Radiol 2019;49:1433-40.
- Park JR, Bagatell R, Cohn SL, et al. Revisions to the International Neuroblastoma Response Criteria: A Consensus Statement From the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 2017;35:2580-7.
- Guenther LM, Rowe RG, Acharya PT, et al. Response Evaluation Criteria in Solid Tumors (RECIST) following neoadjuvant chemotherapy in osteosarcoma. Pediatr Blood Cancer 2018;65.
- McHugh K, Kao S. Can paediatric radiologists resist RECIST (response evaluation criteria in solid tumours)? Pediatr Radiol 2003;33:739-43.
PAEDIATRIC CARDIAC IMAGING
Paediatric Cardiac imaging |
Disease |
Biomarker and evidence for use |
Description of imaging technique |
Pathophysiological process informed by MRI biomarker |
Biomarker measured |
Units of measurement |
Suitable for use in clinical trials |
Myocarditis |
Values of T1 native, T2 mapping and ECV in CMR in pediatric patients with myocarditis. |
CMR |
Myocardial inflamation |
CMR relaxation parameter T1 and T2
|
ms |
Normal values in pediatric healthy population |
- Normal values of diameter of Coronary Artery Diameters in pediatric population ( most of them with Congenital Heart Disease) , determined by Prospectively EKG- triggered coronary CT angiography (CCTA).
- Normal values of T1 native, T2 mapping and ECV in CMR in pediatric healthy population.
|
CCTA
CMR |
Diameter coronary arteries
Values in healthy pediatric population
|
Measure in orthogonal plane in coronary arteries
CMR relaxation parameter T1 and T2
|
Mm
ms |
|
Thalassaemia Major |
Value of T2* on CMR for the early identification and treatment of patients at high risk of heart failure and arrhythmia1! |
CMR (direct assessment of myocardial iron concentration with CMR because iron deposits shorten T2*) |
Myocardial siderosis |
CMR relaxation parameter T2* |
ms Cardiac T2* values > 20 ms are considered normal |
- Kirk P, Roughton M, Porter JB et al. Cardiac T2* Magnetic Resonance for Prediction of Cardiac Complications in Thalassemia Major. Circulation 2009;120:1961-1968
PAEDIATRIC LUNG IMAGING
Paediatric lung imaging |
Disease |
Biomarker and evidence for use |
Description of radiology technique |
Pathophysiological process informed by biomarker |
Biomarker measured |
Units of measurement |
|
Cystic Fibrosis Bronchiectasis and airway wall thickening |
CT
|
End-inspiratory or free-breathing non-contrast enhanced CTR |
Key measure in disease progression1-4!, risk of pulmonary exacerbation3,5!, lower QoL |
Severity and extent of bronchiectasis
Airway Tapering |
Score depends on disease and scoring system6-7!: Semiquantitative (Bhalla, Brody, CF-CT), score range from 0-3 (mild-moderate-severe, tubular, varicose and cystic) Intra and inter branches tapering index |
Small Airways Diseases
|
CT |
End-expiratory CT |
Key measure in disease progression1,8,9!, reflecting small airways disease |
Low Attenuation Region (LAR) (LAR/Lungvolume)*100% |
Volume quantified with HU-based software or PRAGMA-CF scoring system7! |
|
Airways – artery ratio |
CT |
End-inspiratory of free-breathing CT non contrast enhanced |
Key measure of bronchiectasis, air wall thickening and lack of tapering |
Inflammation |
Automatic segmentation with software11,12, 13! Fraction of abnormal airways per generation |
|
PRAGMA-CF |
CT |
End-inspiratory and expiratory CT of free-breathing CT non contrast enhanced |
Measure of key CF features, such as bronchiectasis, bronchial wall thickening, mucus plugging, consolidation, air trapping |
Disease progression |
Each feature is express as % of total lung volume or ml |
|
Quantification of lung water |
MR |
Half-Fourier singleshot turbo spin-echo |
Measure the severity of lung disease or pulmonary oedema. |
Monitoring lung disease |
Lung water density (LWD, %) is the ratio of lung to liver signal intensity multiplied by 70%, the estimated hepatic water density16! |
|
Diaphragmatic motion disorders/Diaphragm hernia |
US/MRI |
M-mode sonography of hemidiaphragms during respiratory movements, subxiphoid and subcostal approach
T2- be used for clinical trials
Half-fourier-acqusition single-shot turbo spin-echo (HASTE) , T2- (true fast imaging with steady-state free precession) (TRUFI) at least two planes (coronal, axial or sagittal) |
Key measure in evaluation of hemidiaphragmatic respiratory movements
Key measure is to identify the diaphragm defect, hernia content, mediastinal shift, associated lung abnormalities |
Hemidiaphragmatic excursions, difference of excursions between the hemidiaphragms Severity and extent of the diaphragm defect |
mm, % 14,15!
mm, % |
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- Szczesniak J Cyst Fibros. 2017 Mar;16(2):175-185
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- Kuo J Cyst Fibros. 2017 Jan;16(1):116-123
- Urvoas E Pediatr Radiol 1994;24:564-568
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- Thompson RB Journal of Cardiovascular Magnetic Resonance 2019; 21:58