Jiacheng Wang, Ivana Isgum, Ipek Oguzcs.CV eess.IV
Whole-heart segmentation (WHS) in computed tomography (CT) and magnetic resonance imaging (MRI) is affected by acquisition shifts and heterogeneous cardiac annotations. Existing WHS systems combine architectural design, transfer learning, and generic spatial or intensity augmentation. We investigate whether changes to data augmentation and training supervision can improve cross-modality WHS while the segmentation architecture is held constant. We present LISynSeg, a data-centric approach that augments real-image nnU-Net training with label-to-image synthesis. Synthetic volumes are generated from cardiac label maps using contrast and acquisition perturbations calibrated to the training cohort, then mixed with real images to retain thoracic context absent from the labels (and thus the synthesized images). We model cardiac label variation through controlled changes in myocardial wall thickness and partial supervision of uncertain vessel endpoints. On the CARE Whole-Heart benchmark, synthetic-only training performs worse than the real-image nnU-Net baseline, whereas calibrated real-synthetic training improves cross-modality segmentation without changing the architecture; the improvement is larger for MRI than for CT. The results show that modifying the training data strategy can benefit model development for heterogeneous cardiac data. Code and trained weights will be released at https://github.com/MedICL-VU/Care26_LISynSeg.
Tanish Mudaliar, Justin Li, Daniel Lin +4eess.IV cs.CV
Whole-heart segmentation from CT and MRI is essential for quantitative cardiac image analysis, but remains challenging under multi-center and multi-modality distribution shift. In the CARE whole-heart segmentation task, models must generalize from limited labeled sites to unseen acquisition distributions, where variation in spacing, intensity, reconstruction texture, and anatomy can degrade out-of-distribution performance. We propose a modality-routed 3D cardiac segmentation pipeline that combines TotalSegmentator-initialized nnU-Netv2 models with site-characterized, label-preserving appearance augmentation. We first characterize the available sites using measurable image properties and use this analysis to motivate candidate data-space generalization routes. The final retained recipe applies Bias Field + Bezier appearance augmentation, combining smooth spatial intensity perturbation with nonlinear intensity remapping, followed by lightweight class-wise largest-connected-component cleanup. On the primary held-out-site validation splits, the final configuration improves CT mean Dice from 0.8350 to 0.9135 and MRI mean Dice from 0.7695 to 0.7830, while also reducing HD95. These results suggest that site-motivated appearance augmentation is a practical strategy for improving cross-site robustness in limited-data whole-heart segmentation. Our code can be found in https://github.com/Purdue-M2/Improving-Cross-Site-Whole-Heart-Segmentation
Public cardiac cohorts annotate different subsets of the heart, so shapes from separate sources cannot be pooled without shared correspondence. Among released cardiac shape resources, none we identified carries the atrial appendage, pulmonary veins, and caval stumps as separate blocks in one mesh. Completion benchmarks also compare deep models against a least-squares projection onto shape modes, not the conditional estimator the same fitted model implies. We release an eleven- structure cardiac computed-tomography (CT) statistical shape model, built from 383 automatically labelled cases in 11 571-vertex correspondence, and compare completion estimators under one frozen internal split and endpoint. On a 76-case internal list held out from fitting, a closed-form conditional-Gaussian estimator reconstructed the missing non-chamber structures at 3.717 mm mean per-vertex error, averaged equally over one, three, five, and nine observed structures. A five-refit mask-conditioned graph variational autoencoder reached 5.248 mm and nearest-neighbour retrieval 8.931 mm. The paired difference was 1.531 mm (95% confidence interval 1.384 to 1.711), and the ordering held in a raw-coordinate sensitivity arm. Expert manual labels exist for 58 external CT cases, but our registered reference is close enough to score only five structures. There the closed-form estimator again had lower average surface distance, 95th-percentile Hausdorff distance, and Chamfer error for both completed atria. On a second public benchmark of 20 cases the reference was close enough for three of four completed structures, and the same ordering held there. Four structures have no expert reference. The released model and its completion operator support cohort-unification research on aligned CT, not clinical use.
Full-cycle biventricular geometry is essential for characterizing cardiac function. However, dense and temporally consistent 3D+t biventricular meshes are not routinely available, whereas end-diastolic (ED) anatomy can often be obtained reliably. We therefore investigate full-cycle biventricular motion synthesis from a single ED mesh. This task is challenging because cardiac deformation is spatially heterogeneous and phenotype dependent, while conventional global generative models often obscure localized motion patterns. In this study, we propose a region-specific and phenotype-adaptive framework that integrates motion-informed functional parcellation with conditional latent flow. A functional partition learned from reconstructed motion organizes the ventricular surface into regions with coherent dynamics and enables topology-aware regional feature exchange. A phenotype-conditioned rectified-flow model subsequently maps the ED anatomy to full-cycle motion latents through fine-grained conditioning and prototype-routed motion adapters. An optional control branch further incorporates available motion descriptors for controllable synthesis. Experiments on ACDC, M\&Ms, and M\&Ms-2 demonstrate consistent improvements in geometric accuracy and functional fidelity. Under ED-only synthesis, our method achieves biventricular ASSD, HD95, and vRMSE of \(1.49\pm0.34\)~mm, \(3.77\pm1.06\)~mm, and \(3.31\pm1.03\)~mm, respectively, outperforming all competing methods. Complementary functional and robustness evaluations further demonstrate that the synthesized sequences preserve physiologically plausible ventricular dynamics and generalize across cohorts and disease phenotypes. The code will be released publicly upon acceptance of the manuscript for publication.
Burcu Ozek, Aruna Mohan, David Vorchheimer +5cs.CV cs.LG
Reduced left ventricular ejection fraction (LVEF) is frequently asymptomatic and often detected only after advanced heart failure develops. Electrocardiograms are recorded routinely yet underused for this condition, because reduced LVEF has no single diagnostic waveform. We trained an ensemble of vision transformers from scratch to detect reduced LVEF ($\leq$40%) from 12-lead ECGs, analyzing each heartbeat individually, using 10,142 patients across seven sites in three US health systems. In a held-out external cohort of 4,092 patients from three geographically independent US clinical sites at a real-world reduced-LVEF prevalence of 8.72%, the model achieved an AUROC of 0.88 (95% CI 0.86-0.89), sensitivity 81.2%, specificity 81.0%, and negative predictive value 97.8%. Sensitivity remained high across sex, race, ethnicity, and comorbidity subgroups, while specificity was lower in older patients and those with atrial fibrillation or cardiomyopathy. Beat-level attention maps provided interpretability into the model's predictions, showing consistent focus on the QRS complex rather than the P wave. These findings support the potential of routine ECGs as a scalable first-pass triage step to identify patients who should undergo echocardiography for reduced ejection fraction across diverse patient populations.
Rishov Paul, Frederick H. Epstein, Miaomiao Zhangcs.CV cs.LG
Myocardial strain analysis of cardiac magnetic resonance (CMR) images provides an important tool for evaluating cardiac function. However, current techniques require either human-adjusted post-processing with suboptimal regional accuracy, or specialized and costly imaging acquisitions. In this paper, we propose to leverage the power of generative models to synthesize high-quality motion-derived strain values from routinely acquired CMR sequences. Specifically, we develop a novel Brownian bridge diffusion model in motion space to learn the probabilistic mapping between standard CMR motion estimated from widely adopted registration methods and highly accurate motion provided by advanced strain imaging techniques. To promote the fidelity of anatomical structure in the generation process, our model is conditioned on the corresponding CMR images. We validate our method on large-scale multi-center CMR datasets including subjects of paired standard cine CMR and advanced strain imaging acquisitions. Experimental results demonstrate that our framework significantly improves the accuracy of motion prediction and strain analysis from standard CMRs compared to existing learning-based approaches. Our research represents a new paradigm for potentially developing cost-effective, clinically deployable AI tools for cardiac function assessment with enhanced strain accuracy in busy clinical workflows. Our code is publicly available at anonymous.4open.science/r/Brownian-Bridge-strain-analysis-1140.
Brunnhilde Ponsi, Thomas Carlier, Lara Marteau +5cs.CV cs.LG physics.med-ph
Arrhythmogenic left ventricular cardiomyopathy is a genetic myocardial disease difficult to diagnose due to the lack of gold standard criteria. Simultaneous PET/MR imaging, combined with multiparametric quantitative analysis, could facilitate the identification of different profiles related to the phenotype and progression of cardiomyopathy. This preliminary study focuses on a methodological strategy for dealing with PET/MRI data, including inter-patient data linkage and regional analysis. Two-step clustering was applied to T1 and T2 maps, LGE, and 18F-FDG-PET images of 99 patients genetically diagnosed with arrhythmogenic left ventricular cardiomyopathy. Each patient's images were independently z-scored and summed into a single volume, which was clustered into supervoxels. Thirty-two inter-patient groups of supervoxels were obtained by spectral clustering. An "abnormality" score was assigned to each cluster and modality, and used to visualise abnormal regions likely associated with disease. They enabled the generation of automated textual and bullseye health reports for each patient, which were compared with cardiac imager assessments using balanced accuracy in repeated nested cross-validation. This approach was further validated on a larger cohort of 167 numerical phantoms. The reports generated by clustering accurately identified most of the cardiac physicians' observations (BA = 0.76 $\pm$ 0.04 in repeated nested cross-validation on patients, and BA $\ge$ 0.8 on phantoms). Furthermore, the identified abnormal clusters closely matched their visual observations, facilitating the identification of varying degrees of fibrosis or inflammation on the images. This approach enables a more systematic handling of multimodal PET/MRI data to characterise myocardial heterogeneity in arrhythmogenic left ventricular cardiomyopathy patients.
Deformable shape representations have proven to be robust complements to texture features in cardiac image classification, offering geometric priors that are invariant to imaging artifacts and intensity variations. However, existing deep networks perform simple concatenation to combine these distinct feature representations, which neither fully exploits their complementary nature nor learns cross-modal feature dependencies. Furthermore, this results in uniform attention across all timepoints; hence ignoring the varying diagnostic importance across the cardiac phases. In this paper, we propose a novel cardiac video classification model that, for the first time, learns temporal features in an integrated space of deformable shape and image texture representations. In particular, we design a bi-directional cross-attention in the latent space to fuse latent deformable shape and image features, allowing each modality to adaptively weight the other based on spatio-temporal correspondence. In contrast to current methods that apply uniform weighting across all the cardiac phases, our approach learns to dynamically adjust the contributions of shape and texture representations, derived from images, over time. We demonstrate state-of-the-art classification performance on a cine cardiac magnetic resonance (CMR) video dataset, achieving improved interpretability from attention mechanisms that identify diagnostically critical cardiac phases and modality contributions.
Donghang Lyu, Marius Staring, Yiming Dong +3cs.CV cs.AI
Cardiac cine Magnetic Resonance Imaging (MRI) is a critical diagnostic tool that provides dynamic insights for radiologists. To accelerate acquisition, under-sampled k-space data is often used, requiring reconstruction methods that combine coil sensitivity encoding with prior information to recover missing data. Deep learning approaches have gained more attention for leveraging data-adaptive priors. While supervised learning approaches are a common choice, they depend on fully sampled reference data, which is not always available. Unsupervised methods eliminate the need for fully sampled reference data, which can be advantageous in cardiac cine MRI reconstruction. Among them, implicit neural representations (INRs) have shown great potential due to their simple architecture and good quality reconstructions. In this work, we propose an image-domain dual-branch INR framework, termed I-FP-INR, which extends the original INR design by introducing an additional feature-processing branch. This design aims to extract complementary feature embeddings to enhance the overall representation, thereby benefiting reconstruction. Extensive evaluations on both public datasets and in-house data show consistent improvements over baseline methods in reconstruction quality, with strong robustness across varied scenarios.
Real-time cardiac cine MRI enables visualization of the beating heart during free breathing, but severe undersampling and motion make reconstruction highly challenging. A central challenge for reconstruction is incorporating powerful priors of cardiac anatomy while remaining computationally efficient. We propose Piecewise Dynamic Diffusion Regularization (PDDR), a reconstruction method that integrates a spatiotemporal diffusion model as a generative prior within a variational reconstruction framework for cine MRI. The model employs dedicated spatial layers to encode anatomical structure and temporal layers to capture cardiac motion learned from gated cine data. PDDR leverages the dynamic prior in a piecewise manner, enabling the efficient use of spatiotemporal diffusion models for processing of long real-time sequences. Experiments on retrospectively accelerated and prospective real-time cine MRI demonstrate that PDDR outperforms classical, unsupervised, and diffusion-based methods, delivering high-quality reconstructions with substantially reduced computation time compared to state-of-the-art baselines. These results highlight PDDR as a practical and scalable solution for free-breathing, real-time cardiac MRI. Code is available at https://github.com/MLI-lab/pddr.
Clinical cardiac imaging pipelines currently deploy separate models for each dataset and modality, incurring redundant training costs and precluding knowledge sharing across anatomically related tasks. Consolidating semi-supervised learning, unsupervised domain adaptation, and domain generalisation into one model is therefore a practical necessity, yet naive joint training exposes a fundamental barrier: conflicting label semantics between datasets collapse LA Dice from 90.31\% to 83.38\%, while gradient imbalance across tasks of unequal complexity suppresses the weaker tasks throughout training. We present UniT-Diff, a unified diffusion segmentation framework that resolves these conflicts through three targeted mechanisms. An 11-channel task-specific output space physically partitions label categories, eliminating cross-task gradient sign reversal by construction. SNR-Adaptive Task Conditioning (SATC) scales the task token by the log signal-to-noise ratio of the current diffusion timestep, suppressing domain-specific bias during coarse denoising and restoring full task guidance as the signal clears. Task-Type-Aware Conditional Dropout (TTACD) permanently removes the task token for domain-generalisation inputs, routing them through a shared neutral pathway that draws on cross-dataset cardiac anatomy rather than source-vendor statistics. Under a single parameter set, UniT-Diff surpasses independently trained task-specific baselines on all three benchmarks simultaneously: +0.87\% on LA, +1.77\% on MMWHS, and +0.88\% on MNMS.
Accurate 4D whole-heart mesh reconstruction from sparse cine MRI is critical for creating cardiac digital twins, but remains challenging due to limited 2D slice coverage and the complex coupling between cardiac shape and motion. Existing methods often rely on intermediate contour fitting and typically reconstruct static, single-phase, or partial cardiac geometries, limiting their ability to capture full-chamber dynamics. We propose a novel end-to-end framework for reconstructing temporally resolved whole-heart meshes from multi-view 2D cine MRI sequences by learning an image-to-mesh mapping. The framework incorporates a differentiable contour renderer inspired by the Beer-Lambert attenuation principle, enabling anatomy-aware supervision of 3D+t mesh deformation through contour-based projection losses. To improve temporal consistency across the cardiac cycle, we further introduce a multi-scale temporal modeling module that integrates global cycle-level dynamics with local inter-frame coherence to generate smooth and physiologically plausible mesh trajectories. The proposed method achieved a whole-heart mean absolute error of 1.68 $\pm$ 0.31 mm and a motion jitter of 0.77 $\pm$ 0.17 $\mathrm{mm}/\mathrm{frame}^{3}$, outperforming existing methods with lower reconstruction error and substantially improved motion smoothness. It also improved 2D contour alignment across multiple cine MRI views and supported downstream proof-of-concept electrophysiological simulation. The code will be released publicly upon acceptance of the manuscript for publication.
Francesco Fabbri, Martino Andrea Scarpolini, Paolo Ciancarella +4cs.CV cs.AI q-bio.TO
Computational models of the human heart are widely used to study electromechanical and fluid-dynamical cardiac function and to support applications such as in silico clinical trials. However, most studies remain limited to single or patient-specific anatomies, restricting the inclusion of population-level variability required for uncertainty quantification. A key challenge is translating medical-image segmentations, which may contain artifacts, mesh defects or disjoint domains, into topologically coherent geometries suitable for multiphysics simulations. In this work, we present a semi-automatic pipeline that converts CT-based segmentations into simulation-ready cardiac meshes within a few minutes while preserving anatomical and topological consistency. Building on modern deep learning segmentation methods, the framework incorporates a template-based registration stage to regularize artifacts and enforce mesh-quality constraints. A Chamfer-distance morphing strategy deforms a high-quality template toward each segmented heart, matching individual chambers while preserving topology. The resulting meshes are watertight, isotopological, and endowed with consistent point-to-point correspondence. The pipeline is validated on 58 healthy cardiac CT scans, including all cardiac chambers and proximal vessel segments. The resulting meshes can be represented in a unified shape space, enabling the construction of a statistical shape model of the heart and major vessels. Principal Component Analysis shows that a low-dimensional latent space efficiently captures population variability, while Gaussian Mixture Modeling enables synthetic anatomy generation. Overall, the proposed framework (released open-source) provides a pathway from raw segmentations to simulation-ready cardiac geometries, enabling anatomically consistent virtual cohorts for large-scale in silico studies.
Identifying robust associations between cardiac imaging phenotypes and clinical diseases is fundamental to population-scale cardiovascular research and reliable risk stratification. However, current phenome-wide association studies rely on pre-defined, single-variable phenotypes or expert-crafted features, which limits their ability to capture clinically meaningful non-linear effects and cross-phenotype interactions. To address this, we propose CPAgents, an iterative phenotype-Composition framework for cardiovascular Phenome-wide association study (PheWAS) that automatically constructs and validates interpretable composite phenotypes (e.g., polynomial, ratio, and interaction forms) from base imaging features. Specifically, our system coordinates three agents: (i) an Analyst that identifies statistical pathologies and nominates candidate transformations; (ii) a Proposer that generates constrained, medically and statistically motivated expressions under numerical safety rules; and (iii) a Verifier that evaluates candidates using multi-stage criteria and produces transparent evidence trails for accepted phenotypes. Evaluated on a population-scale cardiac imaging cohort, the discovered composite phenotypes markedly improve disease discrimination: across 72 classifier-disease-metric combinations, our variants achieve the top rank in 56 cases versus 18 for baselines, with gains observed across all nine clinical disease categories. Our framework yields compact, clinically interpretable phenotype formulas with transparent evidence trails, enabling scalable discovery of stronger phenotype-disease associations beyond expert-driven feature selection.
Abhishek H S, Akash Ganamukhi, Abhimanyu Suresh +3cs.CV cs.AI
Building patient-specific cardiac models sits at the heart of precision cardiology, yet getting those models into clinical use keeps running into the same wall: mesh generation is slow, messy, and frustrating. The standard workflow -- segmenting the image, running Marching Cubes, and then manually cleaning up the result -- is time-consuming, inconsistent across operators, and demands specialist knowledge most clinical teams do not have. We take a fundamentally different approach. Instead of treating segmentation and mesh generation as two separate problems, we train a single end-to-end network that goes directly from a raw 3D medical image to a smooth, simulation-ready cardiac surface mesh. The core is a 3D Swin Transformer encoder-decoder that extracts volumetric features from CT or MRI volumes, paired with a Graph Attention Network (GAT) head that iteratively deforms a template mesh to fit the patient's cardiac boundary. We tested on the MM-WHS 2017 benchmark using both CT and MRI. Segmentation scores were competitive (Dice of 0.84 on CT, 0.83 on MRI), but the primary focus is mesh quality: mean Chamfer distance of 1.8 mm, with 95th-percentile surface distance below 5 mm. Every mesh is produced in a single forward pass -- no Marching Cubes, no smoothing filters, no manual cleanup. We argue that for cardiac digital twin pipelines, geometric fidelity and topological correctness matter more than pixel-level Dice scores. By removing the post-processing bottleneck, this approach makes patient-specific cardiac simulation substantially more accessible for clinical use.
In-silico trials of medical devices require the generation of virtual populations of anatomies. In cardiovascular applications, virtual anatomy is typically represented as a 3D+t mesh sampled from a generative model. However, most existing mesh generators focus on static anatomy, while sequence models often lack explicit periodicity. To this end, we propose 4D F-MeshLDM, a conditional generative framework comprising a convolutional mesh VAE to encode meshes, a structural latent space that parameterises motion using a truncated Fourier series, and a diffusion prior that learns the latent distribution over Fourier coefficient tokens. By conditioning the diffusion process on clinical covariates via affine modulation, we enable controllable synthesis. Sampling tokens and performing inverse Fourier synthesis yield cycle-consistent latent trajectories, which can be decoded into 3D+t cardiac mesh sequences. Experiments on 5,000 UK Biobank subjects demonstrate that 4D F-MeshLDM outperforms state-of-the-art baselines in anatomical fidelity and achieves near-zero cycle closure error. Furthermore, the generated cohorts accurately preserve clinical functional indices, highlighting the potential of our framework for reliable in-silico cardiac trials.
Accurate 3D geometric characterization of myocardial infarction (MI) is essential for building cardiac digital twins (CDTs) to precisely simulate infarct-related electrophysiology. Late gadolinium enhancement magnetic resonance imaging (LGE MRI) is the clinical reference for locating MI, yet its reliance on contrast agents restricts use in renally impaired patients and limits longitudinal follow-ups. As an alternative, contrast-free cine MRI visualizes abnormal ventricular wall motion, which is highly indicative of the infarcted area. In this study, we propose a novel explicit geometry-motion embedded model to fully automatically reconstruct personalized, simulation-ready 3D MI geometries directly from multi-view cine MRIs. Specifically, we construct a 4D (3D + t) biventricular mesh to explicitly extract and decouple geometry-aware and motion-aware features. We further design a dual-branch module for adaptive geometry-motion fusion to capture spatiotemporal dependencies for mapping infarcted region. Furthermore, we introduce multi-scale supervision utilizing an AHA-17 segment-guided cross-attention mechanism to steer the prediction, ensuring biophysically consistent reconstruction. Experimental results on 225 cine MRIs demonstrated that the proposed 3D MI reconstruction achieved high performance with an average Dice score of 0.678 $\pm$ 0.011. In the downstream in-silico electrophysiological simulation evaluations, the results were highly consistent with the LGE-derived ground truth, highlighting the great potential of the proposed model for contrast-free scar characterization and seamless integration into CDT modeling. The code will be released publicly upon acceptance of the manuscript for publication.
Reconstructing 4D (3D+t) cardiac geometry from sparse 2D echocardiography is highly desirable yet fundamentally challenged by geometric ambiguity and temporal discontinuity. To tackle these issues, we propose Echo4DIR, a novel test-time 4D implicit reconstruction framework. Specifically, we learn robust 3D shape priors from statistical shape models (SSMs) via a cardiac conditional SDF, constructing an Epipolar Mask Encoder module with epipolar cross attention to effectively fuse multi-view features. To bridge the synthetic-to-real domain gap, we introduce a self-supervised SDF-tailored differentiable rendering strategy for patient-specific 3D shape adaptation using uncalibrated clinical masks without requiring 3D ground truth. Crucially, the inherent continuity of implicit representation overcomes sparse observations, enabling anatomically reliable geometry at arbitrary resolutions. Furthermore, to empower our framework with physically continuous 4D extension, we introduce a Radial SDF Alignment strategy that strictly locks shape evolution to the predicted velocity field, fundamentally eliminating mesh drift. Extensive experiments on synthetic benchmarks and real clinical datasets demonstrate that Echo4DIR achieves state-of-the-art 4D cardiac mesh reconstruction, notably yielding an impressive clinical overlap of up to 98.35% Dice and 96.75% IoU.
Mahmut Yurt, Kanghyun Ryu, Zhitao Li +8eess.IV cs.LG
Conventional cardiac cine MRI relies on breath-hold Cartesian acquisitions, which are vulnerable to motion artifacts and can be uncomfortable or infeasible, particularly for pediatric and other noncompliant patients who cannot reliably hold their breath. Free-breathing radial acquisitions can alleviate these limitations, but robust reconstruction at high acceleration remains challenging due to prominent streak artifacts. To address these limitations, we propose Cine-DL, a clinically oriented framework that couples targeted k-space preprocessing with fast, model-based deep reconstruction. In this pipeline, raw free-breathing radial data undergo retrospective cardiac binning and respiratory gating to resolve cardiac phases and discard motion-corrupted spokes. We then introduce Streak Optimized Coil Compression (SOC), which explicitly preserves cardiac signals while suppressing peripheral interference that typically drives the streak artifacts. The resulting 2D+t cine series is reconstructed with an unrolled network that alternates a ResNet proximal operator with physics-based data consistency updates solved via conjugate gradient. We further employ a memory-efficient training strategy that reduces peak memory usage. We evaluate Cine-DL on free-breathing volunteer data against established baselines (k-t SENSE and iGRASP) and demonstrate clinical translation via hospital deployment on newly acquired patient data. Our experiments show that Cine-DL consistently improves quantitative metrics and visual fidelity, supporting a practical route toward routine, time-sensitive clinical adoption of free-breathing cine MRI.
Clinical fusion of Single Photon Emission Computed Tomography Myocardial Perfusion Imaging (SPECT MPI) and Computed Tomography Angiography (CTA) remains limited by cross-modality misregistration and reliance on manual landmarks, which can hinder accurate ischemia localization and lesion-level functional assessment. To address this issue, we propose a registration and fusion framework for SPECT MPI and CTA that integrates functional and structural information for comprehensive cardiac evaluation. The proposed pipeline performs U-Net-based segmentation on both modalities. On SPECT MPI, only the left ventricle (LV) is extracted, and anatomical landmarks are automatically derived from characteristic LV structures. On CTA, both ventricles are segmented, and their spatial relationship is used to automatically define landmarks at the interventricular septal junction. Scale-space consistency preprocessing and landmark-driven coarse registration are applied to mitigate initial misalignment. Based on this initialization, multiple fine registration methods are evaluated on LV epicardial surface point clouds, including ICP, SICP, CPD, CluReg, FFD, and BCPD-plus-plus. The resulting transformations are then propagated to voxel-level resampling for high-precision SPECT-CTA fusion. In a retrospective cohort of 60 patients, the proposed framework preserved sub-millimeter coronary detail from CTA while accurately overlaying quantitative SPECT perfusion. Among the evaluated methods, BCPD-plus-plus achieved the highest accuracy with a mean point cloud distance of 1.7 mm. By combining robust initialization, comparative fine registration, and voxel-level fusion, the proposed approach provides a practical solution for myocardial ischemia localization and functional evaluation of coronary lesions, while remaining independent of any specific fine registration algorithm.