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Insights into Imaging

Table 1 Imaging biomarkers for disease detection (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)

Disease detection
  Biomarker SemiQ/Q Disease Question answered Utility of biomarker Data from Potential decision for
Non-malignant disease LVEF-US
LVEF-MRI 		Q Cardiac function [28, 29]
Cardiac function 		Cardiac output
Cardiac output 		ICC US 0.72, single centre sensitivity 69% [29]
ICC MRI 0.86,correlation of MRI and cineventriculography 0.72 [99] 		Single centre US
Multicentre MRI [99, 100] 		Inotropes
Inotropes
Renal volume-US, CT, MRI Q Renal failure Mass of parenchyma ICC on US 0.64–0.86 [101]
Correlation of US with CT 0.76–0.8 [102]
Interobserver reproducibility on MRI 87–88% [103] 		Single centre Renal replacement, safety and toxicity of other pharmaceuticals
Young’s modulus on elastography-US Q Thyroid [104], breast [50] and prostate cancer [51]
Parkinson’s disease 		Tumour presence
Muscle stiffness 		Thyroid sensitivity 80%, specificity 95% [104]
Breast AUC 0.898 for conventional US, 0.932 for shear wave elastography, and 0.982 for combined data [105]
Prostate sensitivity 0.84, spec 0.84 [51] 		Thyroid, breast: single centre
Prostate meta-analysis 		Treatment with surgery/radiotherapy/chemotherapy
Lung tissue density Q Emphysema [106, 107] and fibrosis [58] Airways obstruction, interstitial lung disease present Emphysema (density assessment) influences BODE (body mass index, airflow obstruction, dyspnea and exercise capacity) index.
Odds ratio of interstitial lung abnormalities for reduced lung capacity 2.3 		Multicentre
Single centre 		Surgery, valve and drug treatment
Fibrosis and ground-glass index on CT lung SQ Idiopathic lung fibrosis Development of inflammation and fibrosis Mortality predicted by pulmonary vascular volume (HR 1.23 (1.08–1.40), p = 0.001) and honeycombing (HR 1.18 (1.06–1.32), p = 0.002) [108] Single centre Drug treatment
ADC/pCT SQ Ischaemic stroke Presence of salvageable tissue versus infarct core Measure of infarct core/penumbra used for patient stratification for research [109] Planned multicentre Treatment
Malignant disease Lung RADS, PanCan, NCCN criteria [110, 111] SQ Lung nodules Risk of malignancy AUC for malignancy 0.81–0.87 [110] Multicentre Time period of follow-up or surgery
CT blood flow, perfusion, permeability metrics Q Malignant neck lymph nodes
Hepatocellular cancer 		Tumour presence Sensitivity 0.73, specificity 0.70 [112]
AUC 0.75, sensitivity 0.79, specificity 0.75 [113] 		Single centre
Single centre 		Staging and management (surgery, radiotherapy or chemotherapy)
BI-RADS [114]
PI-RADS [115]
LI-RADS [116] 		SQ Cancer Risk of malignancy PPV: BI-RADS0 14.1 %, BI-RADS4 39.1 % and BI-RADS5 92.9 %
PI-RADS2 pooled sensitivity 0.85, pooled specificity 0.71
Pooled sensitivity for malignancy 0.93 		Dutch breast cancer screening programme
Meta-analysis
Systematic review 		Staging and management stratification (surgery, radiotherapy, chemotherapy, combination)
ADC Q Cancer [117]
Liver lesions [118]
Prostate cancer [119] 		Tumour presence Liver AUC 0.82–0.95
Prostate AUC 0.84 		Single centre
Single centre 		Staging and management stratification (surgery, radiotherapy, chemotherapy, combination)
Dynamic contrast enhanced metrics (Ktrans, Kep, blood flow, Ve) Q Liver tumour
Recurrent glioblastoma 		  Hepatocellular cancer AUC 0.85, sensitivity 0.85, specificity 0.81 [113]
Brain- KtransAccuracy 86% [120] 		Single centre
Single centre 		Further treatment
18 FDG SUV Q Cancer
Sarcoma [121]
Lung cancer [105] 		Tumour presence Sarcoma—sensitivity 0.91, specificity 0.85, accuracy 0.88
Lung—sensitivity 0.68 to 0.95 depending on histology 		Meta-analysis
Meta-analysis 		Staging and management stratification (surgery, radiotherapy, chemotherapy, combination)
Targeted radionuclides
[122]In-octreotide [123]
[68]Ga DOTATOC and [68]Ga DOTATATE [124, 125] [68]Ga PSMA [4] 		Non-Q Cancer Tumour presence Sensitivity 97% and specificity 92% for octreotide [126]
Sensitivity 100% and specificity 100% for PSMA [127] 		Single centre
Single centre 		Validation remains difficult because of biopsying multiple positive sites.
  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
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