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Table 2 Imaging biomarkers for disease characterisation (semi-quantitative and quantitative) with examples of current evidence for their use that would support decision-making

From: Validated imaging biomarkers as decision-making tools in clinical trials and routine practice: current status and recommendations from the EIBALL* subcommittee of the European Society of Radiology (ESR)

  Biomarker SemiQ/Q Disease Question answered Utility of biomarker Data from Potential decision for
Non-malignant disease Young’s modulus Q Coronary plaques [53] Risk of rupture Reproducibility CoV 22% vessel wall, 19% in plaque. AUC for focal neurology Youngs modulus + degree = 0.78 Single centre Stenting, coronary bypass surgery
Plaque density, vessel luminal diameter Q Coronary artery stenosis Risk of plaque rupture; risk of significant cardiac ischaemia, infarction, death No luminal narrowing but with coronary artery calcium (CAC) score > 0 had a 5-year mortality HR 1.8 compared with those whose CACS = 0. No luminal narrowing but CAC ≥ 100 had mortality risks similar to individuals with non-obstructive coronary artery disease [138]
CT angiography significantly better at predicting events than stress echo/ECG [68]
Coronary death/non-fatal myocardial infarction was lower in patients with stable angina receiving CT angiography than in the standard-care group (HR = 0.59) [69]
Multicentre
Multicentre
Multicentre
Statins, stenting, coronary bypass surgery
18F-Na SQ Aortic valve disease
Coronary plaque [139]
Acute events from abdominal aortic aneurysm
Valve stenosis present
Likelihood of plaque rupture
Likelihood of aneurysm rupture
Reproducibility NaF uptake 10% [140]
Baseline 18F-NaF uptake correlated closely with the change in calcium score at 1 year [141]
18F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1.61–2.17]) associated with ruptured plaques and those with high-risk features [142]
Aneurysms in the highest tertile of 18F-NaF uptake expanded 2.5× more rapidly than those in the lowest tertile and were 3× more likely to rupture [143]
Single
Multicentre
Coronary stenting, aneurysm stenting
MTR Q Multiple sclerosis Disease progression MTR significantly correlates with T2 lesion volume [144]
Grey matter MTR histogram peak height and average lesion MTR percentage change after 12 months independent predictors of disability worsening at 8 years [145]
Change in brain MTR specificity 76.9% and PPV 59.1% for Expanded Disability Status Scale score deterioration [146]
Multicentre
Single centre
Single centre
Timing of therapeutic intervention
Malignant disease 18 FDG-SUV Q Cancer
Oesophageal cancer
Good or poor prognosis tumour in terms of PFS and OS Wide variation between individuals and tumours [147]
Oesophageal cancer HR 1.86 for OS, 2.52 for DFS [148]
Meta-analysis Neoadjuvant or adjuvant therapy or treatment modality combinations
18FLT-SUV Q Cancer High proliferative activity present Sizeable overlap in values with normal proliferating tissues [75] Review of data from single centre studies Neoadjuvant or adjuvant therapy or treatment modality combinations
ADC
MRF (ADC, T1 and T2)
Q
Q
Q
Cancer, correlates with tumour grade Risk of recurrence or metastasis Area under ROC, sensitivity and specificity of nADCmean for G3 intrahepatic cholangiocarcinoma versus G1+G2 were 0.71, 89.5% and 55.5% [149]
“Unfavourable” ADC in cervix cancer predictive of disease-free survival (HR 1.55) [150]
ADC and T2 together give AUC of 0.83 for separating high- or intermediate-grade from low-grade prostate cancer [151]
Single centre
Meta-analysis
Single centre
Need of biopsy or other invasive diagnosis
Neoadjuvant or adjuvant therapy
Decision for radical treatment or active surveillance
DSC-MRI SQ (rCBV) Brain cancer Grading glioma AUC = 0.77 for discriminating glioma grades II and III [152] Meta-analysis Type and time of intervention/treatment
APT Q Glioma Proliferation APT correlates with tumour grade and Ki67 index [153] Single centre Therapeutic strategies
DCE-CT parameters
Blood flow, permeability
Q Rectal cancer
Lung cancer
  Blood flow 75% accuracy for detecting rectal tumours with lymph node metastases [154]
CT permeability predicted survival independent of treatment in lung cancer [155]
Single centre
Single centre
Surgical dissection, adjuvant radiotherapy
Adjuvant therapy
DCE-MRI parameters Q Cervix cancer
Endometrial cancer
Rectal cancer
Breast cancer
Risk of recurrence or metastasis, survival Tumour volume with increasing signal is a strong independent prognostic factor for DFS and OS in cervical cancer [156]
Low tumour blood flow and low rate constant for contrast agent intravasation (kep) associated with high-risk histological subtype in endometrial cancer [157]
Ktrans, Kep and Ve significantly higher in rectal cancers with distant metastasis [158]
Ktrans, iAUCqualitative and ADC predict low-risk breast tumors (AUC of combined parameters 0.78)
Single centre
Single centre
Single centre
Single centre
Neoadjuvant, adjuvant or multimodality treatment strategies
Radiomic signature [159] Q Multiple tumour types [160, 161] Tumour with good or poor prognosis Data endpoints, feature selection techniques and classifiers were significant factors in affecting predictive accuracy in lung cancer [162]
Radiomic signature (24 selected features) is significantly associated with LN status in colorectal cancer [163]
Single centre
Single centre
Neoadjuvant or adjuvant treatment, immunotherapy
Lymph node dissection, adjuvant treatment
  1. Biomarkers used visually in the clinic are given in italics, and those that are used quantitatively are in bold
  2. Abbreviations: ADC apparent diffusion coefficient, APT amide proton transfer, AUC area under curve, BI-RADS breast imaging reporting and data systems, CBV cerebral blood volume, CoV coefficient of variation, CR complete response, CT computerised tomography, DCE dynamic contrast enhanced, DFS disease-free survival, DOTATOC DOTA octreotitide, DOTATATE DOTA octreotate, DSC dynamic susceptibility contrast, ECG electro cardiogram, FDG fluorodeoxyglucose, FLT fluoro thymidine, HR hazard ratio, HU Hounsfield unit, ICC intraclass correlation, IQR interquartile range, LVEF left ventricular ejection fraction, MRF magnetic resonance fingerprinting, MRI magnetic resonance imaging, MTR magnetisation transfer ratio, NCCN National Comprehensive Cancer Network, OS overall survival, pCT perfusion computerised tomography, PERCIST positron emission tomography response criteria in solid tumours, PD progressive disease, PFS progression-free survival, PPV positive predictive value, PI-RADS prostate imaging reporting and data systems, PR partial response, PSMA prostate-specific membrane antigen, RECIL response evaluation in lymphoma, RECIST response evaluation criteria in solid tumours, ROC receiver operating characteristic, SD stable disease, SUV standardised uptake value, SWE shear wave elastography, US ultrasound