Estimation of fine-scale histologic features at low magnification

Context. - Whole-slide imaging has ushered in a new era of technology that has fostered the use of computational image analysis for diagnostic support and has begun to transfer the act of analyzing a slide to computer monitors. Due to the overwhelming amount of detail available in whole-slide images, analytic procedures - whether computational or visual - often operate at magnifications lower than the magnification at which the image was acquired. As a result, a corresponding reduction in image resolution occurs. It is unclear how much information is lost when magnification is reduced, and whether the rich color attributes of histologic slides can aid in reconstructing some of that information. Objective. - To examine the correspondence between the color and spatial properties of whole-slide images to elucidate the impact of resolution reduction on the histologic attributes of the slide. Design. - We simulated image resolution reduction and modeled its effect on classification of the underlying histologic structure. By harnessing measured histologic features and the intrinsic spatial relationships between histologic structures, we developed a predictive model to estimate the histologic composition of tissue in a manner that exceeds the resolution of the image. Results. - Reduction in resolution resulted in a significant loss of the ability to accurately characterize histologic components at magnifications less than 310. By utilizing pixel color, this ability was improved at all magnifications. Conclusions. - Multiscale analysis of histologic images requires an adequate understanding of the limitations imposed by image resolution. Our findings suggest that some of these limitations may be overcome with computational modeling.