Synthesizing Post-Acetazolamide Cerebral Blood Flow Maps from Baseline MRI in Moyamoya Using 3D Generative AI
Authors: Julia Huang, Camila Gonzalez, Rydham Goyal, Aja Zou, Sasha Alexander, Michael Moseley, Moss Y. Zhao, Gary K. Steinberg
Organizations: Department of Computer Science, Stanford School of Engineering, Stanford, CA 94305 · Department of Radiology, Stanford School of Medicine, Stanford, CA 94305 · Department of Anesthesia, Intensive Care Medicine, and Pain Medicine, Medical University of Vienna, Vienna, Austria 1090 · Department of Neurosurgery, Stanford School of Medicine, Stanford, CA 94305
For patients with Moyamoya disease, impaired cerebrovascular reserve (CVR) is an important hemodynamic criterion for recommending extracranial-to-intracranial bypass surgery. Standard CVR assessment in this cohort uses paired arterial spin labeling (ASL) perfusion MRI acquired before and after acetazolamide (ACZ). When ACZ is contraindicated or avoided, the post-ACZ cerebral blood flow (CBF) map needed for hemodynamic assessment is unavailable. We propose CAE3D, a deterministic 3D conditional autoencoder that synthesizes post-ACZ CBF maps directly from pre-ACZ ASL input. We evaluated CAE3D against ten comparators, including deterministic and diffusion-style 3D baselines, a 2D contextual baseline, and frozen-encoder foundation-model adapters. CAE3D achieved the lowest held-out MAE (0.066), with SSIM 0.80 and PSNR 24.0 dB, and near-zero full-brain mean bias. Its MAE advantage was statistically significant over seven of eight trained-from-scratch baselines, excluding the 2D CAE_2D comparator; its SSIM and PSNR advantages were significant over all eight. Regional delta-CBF predictions compressed the dynamic range in high-response territories. These results establish the retrospective feasibility of post-ACZ CBF synthesis in patients who completed the standard two-scan protocol. Extension to ACZ-contraindicated patients, who were not represented in this cohort, requires external and prospective validation.
Figures & tables
Figure 1: Established clinical pathway. The protocol used in this cohort requires two ASL scans (pre- and post-ACZ) bracketing an intravenous acetazolamide administration.
Figure 2: Retrospective synthesis task evaluated in this study. CAE3D predicts an independently normalized post-ACZ map from the pre-ACZ input. This diagram illustrates the potential future workflow motivation, not a clinically validated replacement for ACZ imaging.
Figure 3: CAE3D architecture. Skip-connected 3D encoder-decoder (three downsampling levels).
Figure 4: Image context. Pre-ACZ, post-ACZ GT, and post-minus-pre change (middle axial slice, one subject). Image panels use intensity windowing for visualization ( vmax set to the 99th percentile of non-zero voxels); see the plotting scripts in the supplementary material for exact details.
Figure 5: Vascular territory atlas ( Liu et al., 2023 ) on a representative pre-ACZ slice; defines regional summaries (§ 3.4 ). Windowed for visualization as in Figure 4 .
Figure 6: Qualitative reconstruction (CAE3D, held-out test set): best, median, worst PSNR subjects (top to bottom). Columns: pre-ACZ, prediction, GT, error (middle axial slice). Per-subject MAE/SSIM/PSNR in row labels.
Figure 7: Guided backpropagation (CAE3D, one test subject): pre-ACZ, attribution overlay (brighter = stronger influence), GT post-ACZ. Full guided-backpropagation maps are provided in the supplementary material.
Model
Primary seed
Checkpoint-selection rule
CAE3D
42 (predesignated)
Highest validation PSNR, no early stopping
CAE3D-ES
42 (predesignated)
Highest validation PSNR, early stopping (10-epoch plateau)
ResNet_3D
42 (predesignated)
Highest validation PSNR
CAE_2D
42 (predesignated)
Highest validation PSNR
FNO_3D
42 (predesignated)
Highest validation PSNR
Patch_3D
42 (predesignated)
Highest validation PSNR
Table 5: Primary-checkpoint selection rule for each in-house model’s rows in Tables 1 and 6 . Seed 42 was predesignated for every model before training (not chosen post hoc from among the three seeds); within that seed, the checkpoint with the highest validation PSNR was retained, with no test-set involvement in selection. Exact checkpoint filenames and configurations are documented with the code release.
Cine cardiovascular magnetic resonance (CMR) captures the cardiac cycle as a four-dimensional (4D) sequence, but standard acquisition requires electrocardiogram (ECG) gating and repeated breath holds. Visual realism alone does not establish accurate patient-specific ejection fraction (EF) or ventricular volumes. We present PhaseFlow3D, a generative framework that synthesizes a complete 4D cine sequence from a single end-diastolic (ED) three-dimensional (3D) volume without ECG. To capture asymmetric systolic and diastolic dynamics, it represents the cardiac cycle as a piecewise linear phase anchored at ED and end-systolic (ES) time points. At inference, a population-level canonical template supplies this phase without patient-specific temporal information. A phase-conditioned rectified flow model generates a cardiac motion trajectory in latent space. Radial Contraction Decomposition converts each latent state into a 3D displacement field, combining a physics-informed radial component for centripetal myocardial contraction with an image-conditioned residual for rotation and out-of-plane motion. Each frame is generated by directly warping the ED volume, bypassing variational autoencoder decoding. On the combined ACDC and M&Ms benchmark, PhaseFlow3D achieves the lowest EF mean absolute error, the only positive left-ventricular volume-curve R2, and the best distributional quality among compared methods. Ablations confirm each component's contribution. Downstream evaluations demonstrate the utility of the synthesized sequences and displacement fields for segmentation, pathology classification, label propagation, and myocardial strain analysis.
Shiyi Wang, Ruochen Sun, Xiang Li +2
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA · Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA · Center for Advanced Medical Computing and Analysis, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Arterial spin labeling (ASL) perfusion MRI allows direct quantification of regional cerebral blood flow (CBF) without exogenous contrast, enabling noninvasive measurements that can be repeated without constraints imposed by contrast injection. ASL is increasingly acquired in research studies and clinical MRI protocols. Building on successes in structural imaging, recent efforts have implemented deep learning based methods to improve image quality, enable automated quality control, and derive robust quantitative and predictive biomarkers with ASL derived CBF. However, progress has been limited by variable image quality, substantial inter-site, vendor and protocol differences, and limited availability of labeled datasets needed to train models that generalize across cohorts. To address these challenges, we introduce ICHOR, a self supervised pre-training approach for ASL CBF maps that learns transferable representations using 3D masked autoencoders. ICHOR is pretrained via masked image modeling using a Vision Transformer backbone and can be used as a general-purpose encoder for downstream ASL tasks. For pre-training, we curated one of the largest ASL datasets to date, comprising 11,405 ASL CBF scans from 14 studies spanning multiple sites and acquisition protocols. We evaluated the pre-trained ICHOR encoder on three downstream diagnostic classification tasks and one ASL CBF map quality prediction regression task. Across all evaluations, ICHOR outperformed existing neuroimaging self-supervised pre-training methods adapted to ASL. Pre-trained weights and code will be made publicly available.
Xavier Beltran-Urbano, Yiran Li, Xinglin Zeng +10
University of Pennsylvania, Philadelphia, USA · University of Maryland School of Medicine, Baltimore, USA
Generative priors reconstruct accelerated 3D MRI well but pay heavily at deployment: tens of network evaluations per volume, and protocol-specific hyperparameter tuning. A third hidden cost is the scanner's fixed sampling pattern. We treat the whole operating point as an input. A 3D MeanFlow patch network (a one-step flow model) is fine-tuned end-to-end through a warm-started, five-iteration differentiable conjugate-gradient projection. A small hypernetwork maps the operating point (data-consistency weight, acceleration, and the Cartesian sampling pattern itself) to the network's per-channel modulation. Three findings follow. (i) Learning the acquisition is worth more than any other operating point: on clinical knee data, the learned mask gains up to +2.34 dB over the protocol's variable-density mask. This gain requires the solver: with a feed-forward reconstructor the same learned mask hurts at 4x (-1.7 dB), but with the data-consistency projection it adds +4.6 dB. (ii) One evaluation is highly effective: it beats a 20-step patch-diffusion prior by up to +3.1 dB on brain and +2.9 dB on knee. Three to five evaluations extend the front to +6 dB while using a quarter of the prior's network calls. (iii) Fully sampled targets are optional: trained self-supervised on a split of acquired samples, the reconstructor matches its supervised twin at 4x on real data. Finally, we report what failed and why: subject-adaptive acquisition from measured energy, combining self-supervision with learned acquisition, and amortising the data-consistency weight.
Ruibo Wang
Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, 2600 AA Delft, Netherlands