The present invention provides low resolution Raman spectroscopic systems and methods for in-vivo detection and analysis of a lesion in a lumen of a subject. The system uses a multi-mode laser attached to a catheter in making in-vivo Raman spectroscopic measurements of the lumen. The system includes a light collector and/or a light dispersion element as well as a detector to measure spectral patterns that indicate the presence of the lesion. Based on the spectral response of the lumen, the presence (or absence) of a lesion can be determined. In addition, the components of the lesion can also be identified based on the unique Raman spectrum associated with each component.