Mineral Density Volume Gradients in Normal and Diseased Human Tissues

Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

临床计算机断层扫描（Clinical computed tomography）可为包含早晚期病理病变的异质性钙化组织提供单一矿物密度（MD）数值。本研究的创新之处在于，将当前用于绘制矿物密度梯度的定量方法拓展至三维空间，对矿化早晚期阶段进行离散化处理，识别离散化体积内的元素分布，并将测得的矿物密度与对应的钙（Ca）与磷（P）、钙与锌（Zn）的元素比值相关联。为完成上述研究目标，研究将高分辨率台式显微计算机断层扫描（micro-computed tomography, micro-CT）设备借助多色辐射所识别出的矿物密度变化，与通过同步辐射单色光获取的微探针X射线荧光（X-ray fluorescence, XRF）元素成像结果进行了关联。对正常与病变组织（每组5例，受试对象为40~60岁男性）的断层图像进行数字分割后，发现存在显著的矿物密度差异：牙釉质为2820~3095mg/cc；骨组织为570~1415mg/cc；牙骨质为1240~1340mg/cc；牙本质为1480~1590mg/cc；受牙周炎累及的牙骨质为1100~1220mg/cc；矿化不足的龋坏牙本质为345~1450mg/cc；矿化过度的龋坏牙本质为1815~2740mg/cc；牙结石为1290~1770mg/cc。本研究确立了分割后的矿物密度体积与对应体积内元素比值间的合理线性相关性，并观测到牙本质（1.49）、矿化不足牙本质（0.32~0.46）、牙骨质（1.51）与骨组织（1.68）的钙磷比。此外，相较于正常组织，病变适应组织的钙锌比存在差异，如骨组织的钙锌比为855~2765、牙骨质的钙锌比为595~990，这表明锌是介导已观测到的适应性特征的关键元素。综上，本研究结果揭示了矿物密度梯度与元素浓度、元素特征间的关联，可为阐明病理病变形成的机制过程提供参考。