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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)





Question answered

Utility of biomarker

Data from

Potential decision for

Non-malignant disease

Young’s modulus


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


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]




Statins, stenting, coronary bypass surgery



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]



Coronary stenting, aneurysm stenting



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]


Single centre

Single centre

Timing of therapeutic intervention

Malignant disease




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]


Neoadjuvant or adjuvant therapy or treatment modality combinations




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


MRF (ADC, T1 and T2)




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


Single centre

Need of biopsy or other invasive diagnosis

Neoadjuvant or adjuvant therapy

Decision for radical treatment or active surveillance



Brain cancer

Grading glioma

AUC = 0.77 for discriminating glioma grades II and III [152]


Type and time of intervention/treatment





APT correlates with tumour grade and Ki67 index [153]

Single centre

Therapeutic strategies

DCE-CT parameters

Blood flow, permeability


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


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]


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