Krithika Iyer

Krithika Iyer, Alan Morris, Brian Zenger et al.

Statistical shape modeling (SSM) is a valuable and powerful tool to generate a detailed representation of complex anatomy that enables quantitative analysis and the comparison of shapes and their variations. SSM applies mathematics, statistics, and computing to parse the shape into a quantitative representation (such as correspondence points or landmarks) that will help answer various questions about the anatomical variations across the population. Complex anatomical structures have many diverse parts with varying interactions or intricate architecture. For example, the heart is four-chambered anatomy with several shared boundaries between chambers. Coordinated and efficient contraction of the chambers of the heart is necessary to adequately perfuse end organs throughout the body. Subtle shape changes within these shared boundaries of the heart can indicate potential pathological changes that lead to uncoordinated contraction and poor end-organ perfusion. Early detection and robust quantification could provide insight into ideal treatment techniques and intervention timing. However, existing SSM approaches fall short of explicitly modeling the statistics of shared boundaries. This paper presents a general and flexible data-driven approach for building statistical shape models of multi-organ anatomies with shared boundaries that capture morphological and alignment changes of individual anatomies and their shared boundary surfaces throughout the population. We demonstrate the effectiveness of the proposed methods using a biventricular heart dataset by developing shape models that consistently parameterize the cardiac biventricular structure and the interventricular septum (shared boundary surface) across the population data.

Krithika Iyer, Riddhish Bhalodia, Shireen Elhabian

The manifold assumption for high-dimensional data assumes that the data is generated by varying a set of parameters obtained from a low-dimensional latent space. Deep generative models (DGMs) are widely used to learn data representations in an unsupervised way. DGMs parameterize the underlying low-dimensional manifold in the data space using bottleneck architectures such as variational autoencoders (VAEs). The bottleneck dimension for VAEs is treated as a hyperparameter that depends on the dataset and is fixed at design time after extensive tuning. As the intrinsic dimensionality of most real-world datasets is unknown, often, there is a mismatch between the intrinsic dimensionality and the latent dimensionality chosen as a hyperparameter. This mismatch can negatively contribute to the model performance for representation learning and sample generation tasks. This paper proposes relevance encoding networks (RENs): a novel probabilistic VAE-based framework that uses the automatic relevance determination (ARD) prior in the latent space to learn the data-specific bottleneck dimensionality. The relevance of each latent dimension is directly learned from the data along with the other model parameters using stochastic gradient descent and a reparameterization trick adapted to non-Gaussian priors. We leverage the concept of DeepSets to capture permutation invariant statistical properties in both data and latent spaces for relevance determination. The proposed framework is general and flexible and can be used for the state-of-the-art VAE models that leverage regularizers to impose specific characteristics in the latent space (e.g., disentanglement). With extensive experimentation on synthetic and public image datasets, we show that the proposed model learns the relevant latent bottleneck dimensionality without compromising the representation and generation quality of the samples.

Daniel Capellán-Martín, Abhijeet Parida, Zhifan Jiang et al.

Robust and generalizable segmentation of brain tumors on multi-parametric magnetic resonance imaging (MRI) remains difficult because tumor types differ widely. The BraTS 2025 Lighthouse Challenge benchmarks segmentation methods on diverse high-quality datasets of adult and pediatric tumors: multi-consortium international pediatric brain tumor segmentation (PED), preoperative meningioma tumor segmentation (MEN), meningioma radiotherapy segmentation (MEN-RT), and segmentation of pre- and post-treatment brain metastases (MET). We present a flexible, modular, and adaptable pipeline that improves segmentation performance by selecting and combining state-of-the-art models and applying tumor- and lesion-specific processing before and after training. Radiomic features extracted from MRI help detect tumor subtype, ensuring a more balanced training. Custom lesion-level performance metrics determine the influence of each model in the ensemble and optimize post-processing that further refines the predictions, enabling the workflow to tailor every step to each case. On the BraTS testing sets, our pipeline achieved performance comparable to top-ranked algorithms across multiple challenges. These findings confirm that custom lesion-aware processing and model selection yield robust segmentations yet without locking the method to a specific network architecture. Our method has the potential for quantitative tumor measurement in clinical practice, supporting diagnosis and prognosis.

Krithika Iyer, Shireen Y. Elhabian

The study of physiology demonstrates that the form (shape)of anatomical structures dictates their functions, and analyzing the form of anatomies plays a crucial role in clinical research. Statistical shape modeling (SSM) is a widely used tool for quantitative analysis of forms of anatomies, aiding in characterizing and identifying differences within a population of subjects. Despite its utility, the conventional SSM construction pipeline is often complex and time-consuming. Additionally, reliance on linearity assumptions further limits the model from capturing clinically relevant variations. Recent advancements in deep learning solutions enable the direct inference of SSM from unsegmented medical images, streamlining the process and improving accessibility. However, the new methods of SSM from images do not adequately account for situations where the imaging data quality is poor or where only sparse information is available. Moreover, quantifying aleatoric uncertainty, which represents inherent data variability, is crucial in deploying deep learning for clinical tasks to ensure reliable model predictions and robust decision-making, especially in challenging imaging conditions. Therefore, we propose SPI-CorrNet, a unified model that predicts 3D correspondences from sparse imaging data. It leverages a teacher network to regularize feature learning and quantifies data-dependent aleatoric uncertainty by adapting the network to predict intrinsic input variances. Experiments on the LGE MRI left atrium dataset and Abdomen CT-1K liver datasets demonstrate that our technique enhances the accuracy and robustness of sparse image-driven SSM.

Krithika Iyer, Austin Tapp, Athelia Paulli et al.

Quantifying normative pediatric cranial development and suture ossification is crucial for diagnosing and treating growth-related cephalic disorders. Computed tomography (CT) is widely used to evaluate cranial and sutural deformities; however, its ionizing radiation is contraindicated in children without significant abnormalities. Magnetic resonance imaging (MRI) offers radiation free scans with superior soft tissue contrast, but unlike CT, MRI cannot elucidate cranial sutures, estimate skull bone density, or assess cranial vault growth. This study proposes a deep learning driven pipeline for transforming T1 weighted MRIs of children aged 0.2 to 2 years into synthetic CTs (sCTs), predicting detailed cranial bone segmentation, generating suture probability heatmaps, and deriving direct suture segmentation from the heatmaps. With our in-house pediatric data, sCTs achieved 99% structural similarity and a Frechet inception distance of 1.01 relative to real CTs. Skull segmentation attained an average Dice coefficient of 85% across seven cranial bones, and sutures achieved 80% Dice. Equivalence of skull and suture segmentation between sCTs and real CTs was confirmed using two one sided tests (TOST p < 0.05). To our knowledge, this is the first pediatric cranial CT synthesis framework to enable suture segmentation on sCTs derived from MRI, despite MRI's limited depiction of bone and sutures. By combining robust, domain specific variational autoencoders, our method generates perceptually indistinguishable cranial sCTs from routine pediatric MRIs, bridging critical gaps in non invasive cranial evaluation.

Mokshagna Sai Teja Karanam, Krithika Iyer, Sarang Joshi et al.

Spatial transformations that capture population-level morphological statistics are critical for medical image analysis. Commonly used smoothness regularizers for image registration fail to integrate population statistics, leading to anatomically inconsistent transformations. Inverse consistency regularizers promote geometric consistency but lack population morphometrics integration. Regularizers that constrain deformation to low-dimensional manifold methods address this. However, they prioritize reconstruction over interpretability and neglect diffeomorphic properties, such as group composition and inverse consistency. We introduce MORPH-LER, a Log-Euclidean regularization framework for population-aware unsupervised image registration. MORPH-LER learns population morphometrics from spatial transformations to guide and regularize registration networks, ensuring anatomically plausible deformations. It features a bottleneck autoencoder that computes the principal logarithm of deformation fields via iterative square-root predictions. It creates a linearized latent space that respects diffeomorphic properties and enforces inverse consistency. By integrating a registration network with a diffeomorphic autoencoder, MORPH-LER produces smooth, meaningful deformation fields. The framework offers two main contributions: (1) a data-driven regularization strategy that incorporates population-level anatomical statistics to enhance transformation validity and (2) a linearized latent space that enables compact and interpretable deformation fields for efficient population morphometrics analysis. We validate MORPH-LER across two families of deep learning-based registration networks, demonstrating its ability to produce anatomically accurate, computationally efficient, and statistically meaningful transformations on the OASIS-1 brain imaging dataset. https://github.com/iyerkrithika21/MORPH_LER

Nishad Kulkarni, Krithika Iyer, Austin Tapp et al.

Magnetic Resonance Imaging (MRI) is the primary imaging modality used in the diagnosis, assessment, and treatment planning for brain pathologies. However, most automated MRI analysis tools, such as segmentation and registration pipelines, are optimized for healthy anatomies and often fail when confronted with large lesions such as tumors. To overcome this, image inpainting techniques aim to locally synthesize healthy brain tissues in tumor regions, enabling the reliable application of general-purpose tools. In this work, we systematically evaluate state-of-the-art inpainting models and observe a saturation in their standalone performance. In response, we introduce a methodology combining model ensembling with efficient post-processing strategies such as median filtering, histogram matching, and pixel averaging. Further anatomical refinement is achieved via a lightweight U-Net enhancement stage. Comprehensive evaluation demonstrates that our proposed pipeline improves the anatomical plausibility and visual fidelity of inpainted regions, yielding higher accuracy and more robust outcomes than individual baseline models. By combining established models with targeted post-processing, we achieve improved and more accessible inpainting outcomes, supporting broader clinical deployment and sustainable, resource-conscious research. Our 2025 BraTS inpainting docker is available at https://hub.docker.com/layers/aparida12/brats2025/inpt.

Krithika Iyer, Shireen Elhabian

Statistical shape modeling is the computational process of discovering significant shape parameters from segmented anatomies captured by medical images (such as MRI and CT scans), which can fully describe subject-specific anatomy in the context of a population. The presence of substantial non-linear variability in human anatomy often makes the traditional shape modeling process challenging. Deep learning techniques can learn complex non-linear representations of shapes and generate statistical shape models that are more faithful to the underlying population-level variability. However, existing deep learning models still have limitations and require established/optimized shape models for training. We propose Mesh2SSM, a new approach that leverages unsupervised, permutation-invariant representation learning to estimate how to deform a template point cloud to subject-specific meshes, forming a correspondence-based shape model. Mesh2SSM can also learn a population-specific template, reducing any bias due to template selection. The proposed method operates directly on meshes and is computationally efficient, making it an attractive alternative to traditional and deep learning-based SSM approaches.