Piecewise Affine Registration of Biological Images for Volume Reconstruction

This manuscript tackles the reconstruction of 3D volumes via mono-modal registration of series of 2D biological images (histological sections, autoradiographs, cryosections, etc.). The process of acquiring these images typically induces composite transformations that we model as a number of rigid or affine local transformations embedded in an elastic one. We propose a registration approach closely derived from this model. Given a pair of input images, we first compute a dense similarity field between them with a block matching algorithm. We use as a similarity measure an extension of the classical correlation coefficient that improves the consistency of the field. A hierarchical clustering algorithm then automatically partitions the field into a number of classes from which we extract independent pairs of sub-images. Our clustering algorithm relies on the Earth mover’s distribution metric and is additionally guided by robust least-square estimation of the transformations associated with each cluster. Finally, the pairs of sub-images are, independently, affinely registered and a hybrid affine/non-linear interpolation scheme is used to compose the output registered image. We investigate the behavior of our approach on several batches of histological data and discuss its sensitivity to parameters and noise

Prediction of Treatment Response to Neoadjuvant Chemotherapy for Breast Cancer via Early Changes in Tumor Heterogeneity Captured by DCE-MRI Registration.

We analyzed DCE-MR images from 132 women with locally advanced breast cancer from the I-SPY1 trial to evaluate changes of intra-tumor heterogeneity for augmenting early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) after neoadjuvant chemotherapy (NAC). Utilizing image registration, voxel-wise changes including tumor deformations and changes in DCE-MRI kinetic features were computed to characterize heterogeneous changes within the tumor. Using five-fold cross-validation, logistic regression and Cox regression were performed to model pCR and RFS, respectively. The extracted imaging features were evaluated in augmenting established predictors, including functional tumor volume (FTV) and histopathologic and demographic factors, using the area under the curve (AUC) and the C-statistic as performance measures. The extracted voxel-wise features were also compared to analogous conventional aggregated features to evaluate the potential advantage of voxel-wise analysis. Voxel-wise features improved prediction of pCR (AUC = 0.78 (±0.03) vs 0.71 (±0.04), p < 0.05 and RFS (C-statistic = 0.76 ( ± 0.05), vs 0.63 ( ± 0.01)), p < 0.05, while models based on analogous aggregate imaging features did not show appreciable performance changes (p > 0.05). Furthermore, all selected voxel-wise features demonstrated significant association with outcome (p < 0.05). Thus, precise measures of voxel-wise changes in tumor heterogeneity extracted from registered DCE-MRI scans can improve early prediction of neoadjuvant treatment outcomes in locally advanced breast cancer

Colocalization of neurons in optical coherence microscopy and Nissl-stained histology in Brodmann’s area 32 and area 21

Published in final edited form as: Brain Struct Funct. 2019 January ; 224(1): 351–362. doi:10.1007/s00429-018-1777-z.Optical coherence tomography is an optical technique that uses backscattered light to highlight intrinsic structure, and when applied to brain tissue, it can resolve cortical layers and fiber bundles. Optical coherence microscopy (OCM) is higher resolution (i.e., 1.25 µm) and is capable of detecting neurons. In a previous report, we compared the correspondence of OCM acquired imaging of neurons with traditional Nissl stained histology in entorhinal cortex layer II. In the current method-oriented study, we aimed to determine the colocalization success rate between OCM and Nissl in other brain cortical areas with different laminar arrangements and cell packing density. We focused on two additional cortical areas: medial prefrontal, pre-genual Brodmann area (BA) 32 and lateral temporal BA 21. We present the data as colocalization matrices and as quantitative percentages. The overall average colocalization in OCM compared to Nissl was 67% for BA 32 (47% for Nissl colocalization) and 60% for BA 21 (52% for Nissl colocalization), but with a large variability across cases and layers. One source of variability and confounds could be ascribed to an obscuring effect from large and dense intracortical fiber bundles. Other technical challenges, including obstacles inherent to human brain tissue, are discussed. Despite limitations, OCM is a promising semi-high throughput tool for demonstrating detail at the neuronal level, and, with further development, has distinct potential for the automatic acquisition of large databases as are required for the human brain.Accepted manuscrip

Automatic landmark annotation and dense correspondence registration for 3D human facial images

Dense surface registration of three-dimensional (3D) human facial images holds great potential for studies of human trait diversity, disease genetics, and forensics. Non-rigid registration is particularly useful for establishing dense anatomical correspondences between faces. Here we describe a novel non-rigid registration method for fully automatic 3D facial image mapping. This method comprises two steps: first, seventeen facial landmarks are automatically annotated, mainly via PCA-based feature recognition following 3D-to-2D data transformation. Second, an efficient thin-plate spline (TPS) protocol is used to establish the dense anatomical correspondence between facial images, under the guidance of the predefined landmarks. We demonstrate that this method is robust and highly accurate, even for different ethnicities. The average face is calculated for individuals of Han Chinese and Uyghur origins. While fully automatic and computationally efficient, this method enables high-throughput analysis of human facial feature variation.Comment: 33 pages, 6 figures, 1 tabl

Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration.

OBJECTIVE: To quantify the regional and global cerebral atrophy rates and assess acceleration rates in healthy controls, subjects with mild cognitive impairment (MCI), and subjects with mild Alzheimer disease (AD). METHODS: Using 0-, 6-, 12-, 18-, 24-, and 36-month MRI scans of controls and subjects with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we calculated volume change of whole brain, hippocampus, and ventricles between all pairs of scans using the boundary shift integral. RESULTS: We found no evidence of acceleration in whole-brain atrophy rates in any group. There was evidence that hippocampal atrophy rates in MCI subjects accelerate by 0.22%/year2 on average (p = 0.037). There was evidence of acceleration in rates of ventricular enlargement in subjects with MCI (p = 0.001) and AD (p < 0.001), with rates estimated to increase by 0.27 mL/year2 (95% confidence interval 0.12, 0.43) and 0.88 mL/year2 (95% confidence interval 0.47, 1.29), respectively. A post hoc analysis suggested that the acceleration of hippocampal loss in MCI subjects was mainly driven by the MCI subjects that were observed to progress to clinical AD within 3 years of baseline, with this group showing hippocampal atrophy rate acceleration of 0.50%/year2 (p = 0.003). CONCLUSIONS: The small acceleration rates suggest a long period of transition to the pathologic losses seen in clinical AD. The acceleration in hippocampal atrophy rates in MCI subjects in the ADNI seems to be driven by those MCI subjects who concurrently progressed to a clinical diagnosis of AD

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Overcoming the Challenges Associated with Image-based Mapping of Small Bodies in Preparation for the OSIRIS-REx Mission to (101955) Bennu

The OSIRIS-REx Asteroid Sample Return Mission is the third mission in NASA's New Frontiers Program and is the first U.S. mission to return samples from an asteroid to Earth. The most important decision ahead of the OSIRIS-REx team is the selection of a prime sample-site on the surface of asteroid (101955) Bennu. Mission success hinges on identifying a site that is safe and has regolith that can readily be ingested by the spacecraft's sampling mechanism. To inform this mission-critical decision, the surface of Bennu is mapped using the OSIRIS-REx Camera Suite and the images are used to develop several foundational data products. Acquiring the necessary inputs to these data products requires observational strategies that are defined specifically to overcome the challenges associated with mapping a small irregular body. We present these strategies in the context of assessing candidate sample-sites at Bennu according to a framework of decisions regarding the relative safety, sampleability, and scientific value across the asteroid's surface. To create data products that aid these assessments, we describe the best practices developed by the OSIRIS-REx team for image-based mapping of irregular small bodies. We emphasize the importance of using 3D shape models and the ability to work in body-fixed rectangular coordinates when dealing with planetary surfaces that cannot be uniquely addressed by body-fixed latitude and longitude.Comment: 31 pages, 10 figures, 2 table