Recent advances in medical imaging technology have greatly enhanced imaging based diagnosis which requires computational effective and accurate algorithms to process the images (e.g., measure the objects) for quantitative assessment. In this dissertation, one type of imaging objects is of interest: small blobs. Example small blob objects are cells in histopathology images, small breast lesions in ultrasound images, glomeruli in kidney MR images etc. This problem is particularly challenging because the small blobs often have inhomogeneous intensity distribution and indistinct boundary against the background.

This research develops a generalized four-phased system for small blob detections. The system includes (1) raw image transformation, (2) Hessian pre-segmentation, (3) feature extraction and (4) unsupervised clustering for post-pruning. First, detecting blobs from 2D images is studied where a Hessian-based Laplacian of Gaussian (HLoG) detector is proposed. Using the scale space theory as foundation, the image is smoothed via LoG. Hessian analysis is then launched to identify the single optimal scale based on which a pre-segmentation is conducted. Novel Regional features are extracted from pre-segmented blob candidates and fed to Variational Bayesian Gaussian Mixture Models (VBGMM) for post pruning. Sixteen cell histology images and two hundred cell fluorescent images are tested to demonstrate the performances of HLoG. Next, as an extension, Hessian-based Difference of Gaussians (HDoG) is proposed which is capable to identify the small blobs from 3D images. Specifically, kidney glomeruli segmentation from 3D MRI (6 rats, 3 humans) is investigated. The experimental results show that HDoG has the potential to automatically detect glomeruli, enabling new measurements of renal microstructures and pathology in preclinical and clinical studies. Realizing the computation time is a key factor impacting the clinical adoption, the last phase of this research is to investigate the data reduction technique for VBGMM in HDoG to handle large-scale datasets. A new coreset algorithm is developed for variational Bayesian mixture models. Using the same MRI dataset, it is observed that the four-phased system with coreset-VBGMM has similar performance as using the full dataset but about 20 times faster.