As a luminogram, coronary angiography provides a good overview of the coronary artery tree. Using quantitative coronary measurements, the degree of coronary obstruction can be determined. The limitation of coronary angiography is that it does not provide information on the arterial wall structure and therefore cannot assess the extent of atherosclerosis. Knowledge about adaptive coronary remodelling processes as compensatory enlargement of the coronary artery has focused diagnostic interest on the non-stenotic lesions of the coronary tree. Intravascular ultrasound (IVUS) can reveal discrepancies between the extent of coronary atherosclerosis and angiography imaging by in vivo plaque imaging. Spectrum analysis of IVUS-derived radiofrequency (RF) data enables a more detailed analysis of plaque composition and morphology. Preliminary in vitro studies correlated four histological plaque components with a specific spectrum analysis of the RF data. The different components (fibrous, fibrofatty, necrotic core and dense calcium) are colour coded. Coronary tissue maps were reconstructed from RF data using IVUS-Virtual Histology (VH IVUS) software (Real-Time VH, Volcano Corporation, Rancho Cordova, California, USA). VH IVUS has the potential to detect high-risk lesions and can provide new insights into the pathophysiology of coronary artery disease. VH IVUS allows the differentiation of different lesion types based on information derived from histopathology. The in vivo specific histological analysis of coronary atherosclerosis may allow better stratification of treatment of patients with coronary artery disease.