Microcalcification is an indication of vulnerability of plaques in humans. With conventional imaging modalities, screening of micrometer-sized structures in vivo with high spatial resolution has not been achieved. The goal of this study is to evaluate the potentials of micro-computed tomography (micro-CT), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), time-resolved fluorescence spectroscopy (TRFS), scanning acoustic microscopy (SAM), and photoacoustic microscopy (PAM) in the determination of atherosclerotic plaques with microcalcifications and, therefore, the prospect of constructing a modality on a catheter system. The discrimination of microcalcifications within the fibrocalcific plaques and, therefore, the effectivity of these imaging techniques are discussed. The potential of quantum dots (QDs) in biological imaging is also elucidated since they attract great attention as contrast and therapeutic agents, owing unique properties including good light stability, low toxicity, strong fluorescence intensity, and changing emission wavelength with QD size, ranging from 10 to 100 Å in radius.