Calcific aortic valve disease (CAVD) is an active remodeling process associated with pathological mineralization of the collagenous matrix of the valve leaflet, causing a progressive aortic valve leaflet thickening, and eventual disruption of proper valve function. CAVD is the most common valve disease worldwide; in developed countries, it affects up to 25% in those aged >65 years and almost 50% of those aged >85 years. The only available treatment is valve replacement surgery, and, to date no effective pharmacologic treatments have been proven to prevent or counteract the condition. The buildup of mineral in the valve leaflets is highly heterogeneous in its composition and spatial distribution, hence, by quantifying compositional and spatial patterns in valve leaflet lesion we can find clues that correlate with important medical factors. Our long-term goal is to develop therapeutic interventions and targeted drugs based upon our understanding of the mineral and matrix changes of CAVD by correlating such measurable patterns in the microenvironment with the patient’s overall medical history, such as other existing health conditions, or the severity of the disease. I obtained a set of polymethyl methacrylate (PMMA) embedded, calcified human heart valves with their associated patient data. After preliminary 3D scans by mirocomputed tomography (μCT), the leaflets were serially sectioned for staining (Von Kossa and Movat Pentachrome) as well as Fourier Transform Infrared (FTIR) spectroscopy, to obtain hyper spectral maps of valve calcifications and their associated organic matrix across a set of human heart valve samples representing both sexes and ranging from lightly to heavily calcified (as assessed by μCT). After acquiring FTIR maps, I analyzed them using a set of parameters adapted from FTIR bone quality analysis, to examine and calculate spatial patterns in the mineral:matrix ratio, carbonate:phosphate ratio, mineral crystallinity, acid phosphate content, and collagen maturity. These five outcome variables provide a comprehensive picture of mineral and collagen properties and their chemical and spatial heterogeneity in the calcified valve nodule microenvironment. FTIR, additionally, allows us to identify different minerals associated with CAVD, specifically – carbonated hydroxyapatite (HAp, Ca10(PO4)6-x(CO3)x(OH)2-x), and whitlockite (Wh, (CaxMg21-x)H2(PO4)6(OH)2). We found that a higher Wh to HAp ratio correlates spatially with higher amide I absorption, indicating that Wh tends to be found in areas with a lower mineral:matrix ratio and therefore lower overall mineralization. Additionally, I observed that a higher mineral to matrix ratio correlates with a decrease in mineral crystallinity, suggesting that the HAp found in regions with more overall mineralization is more crystalline than the HAp found in less mineralized areas. Lipids tended to be localized in areas with high mineral to matrix ratio, i.e., areas with higher levels of mineralization. Relating these spectroscopic insights to patients’ clinical histories will allow us to explore links between these biomineralogical signatures and the progression of the disease, ultimately facilitating early interventions targeting CAVD.