Functional Imaging Constrained Diffusion for Brain PET Synthesis from Structural MRI (2405.02504v3)
Abstract: Magnetic resonance imaging (MRI) and positron emission tomography (PET) are increasingly used in multimodal analysis of neurodegenerative disorders. While MRI is broadly utilized in clinical settings, PET is less accessible. Many studies have attempted to use deep generative models to synthesize PET from MRI scans. However, they often suffer from unstable training and inadequately preserve brain functional information conveyed by PET. To this end, we propose a functional imaging constrained diffusion (FICD) framework for 3D brain PET image synthesis with paired structural MRI as input condition, through a new constrained diffusion model (CDM). The FICD introduces noise to PET and then progressively removes it with CDM, ensuring high output fidelity throughout a stable training phase. The CDM learns to predict denoised PET with a functional imaging constraint introduced to ensure voxel-wise alignment between each denoised PET and its ground truth. Quantitative and qualitative analyses conducted on 293 subjects with paired T1-weighted MRI and 18F-fluorodeoxyglucose (FDG)-PET scans suggest that FICD achieves superior performance in generating FDG-PET data compared to state-of-the-art methods. We further validate the effectiveness of the proposed FICD on data from a total of 1,262 subjects through three downstream tasks, with experimental results suggesting its utility and generalizability.
- B. H. Ridha, J. Barnes, J. W. Bartlett, A. Godbolt, T. Pepple, M. N. Rossor, and N. C. Fox, “Tracking atrophy progression in familial Alzheimer’s disease: A serial MRI study,” The Lancet Neurology, vol. 5, no. 10, pp. 828–834, 2006.
- B. C. Dickerson, A. Bakkour, D. H. Salat, E. Feczko, J. Pacheco, D. N. Greve, F. Grodstein, C. I. Wright, D. Blacker, H. D. Rosas et al., “The cortical signature of Alzheimer’s disease: Regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals,” Cerebral Cortex, vol. 19, no. 3, pp. 497–510, 2009.
- C. Hohenfeld, C. J. Werner, and K. Reetz, “Resting-state connectivity in neurodegenerative disorders: Is there potential for an imaging biomarker?” NeuroImage: Clinical, vol. 18, pp. 849–870, 2018.
- P. J. Nestor, D. Altomare, C. Festari, A. Drzezga, J. Rivolta, Z. Walker, F. Bouwman, S. Orini, I. Law, F. Agosta et al., “Clinical utility of FDG-PET for the differential diagnosis among the main forms of dementia,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 45, pp. 1509–1525, 2018.
- P. N. Young, M. Estarellas, E. Coomans, M. Srikrishna, H. Beaumont, A. Maass, A. V. Venkataraman, R. Lissaman, D. Jiménez, M. J. Betts et al., “Imaging biomarkers in neurodegeneration: Current and future practices,” Alzheimer’s Research & Therapy, vol. 12, pp. 1–17, 2020.
- C. Domínguez-Fernández, J. Egiguren-Ortiz, J. Razquin, M. Gómez-Galán, L. De las Heras-García, E. Paredes-Rodríguez, E. Astigarraga, C. Miguélez, and G. Barreda-Gómez, “Review of technological challenges in personalised medicine and early diagnosis of neurodegenerative disorders,” International Journal of Molecular Sciences, vol. 24, no. 4, p. 3321, 2023.
- C. Hinrichs, V. Singh, G. Xu, and S. C. Johnson, “Predictive markers for AD in a multi-modality framework: An analysis of MCI progression in the ADNI population,” NeuroImage, vol. 55, no. 2, pp. 574–589, 2011.
- I. M. Nasrallah and D. A. Wolk, “Multimodality imaging of Alzheimer’s disease and other neurodegenerative dementias,” Journal of Nuclear Medicine, vol. 55, no. 12, pp. 2003–2011, 2014.
- R. Wittenberg, M. Knapp, M. Karagiannidou, J. Dickson, and J. M. Schott, “Economic impacts of introducing diagnostics for mild cognitive impairment Alzheimer’s disease patients,” Alzheimer’s & Dementia: Translational Research & Clinical Interventions, vol. 5, pp. 382–387, 2019.
- S. Sharma and P. K. Mandal, “A comprehensive report on machine learning-based early detection of Alzheimer’s disease using multi-modal neuroimaging data,” ACM Computing Surveys, vol. 55, no. 2, pp. 1–44, 2022.
- Y. Pan, M. Liu, Y. Xia, and D. Shen, “Disease-image-specific learning for diagnosis-oriented neuroimage synthesis with incomplete multi-modality data,” IEEE Transactions on Pattern Analysis and Machine Intelligence, vol. 44, no. 10, pp. 6839–6853, 2021.
- S. Hu, B. Lei, S. Wang, Y. Wang, Z. Feng, and Y. Shen, “Bidirectional mapping generative adversarial networks for brain MR to PET synthesis,” IEEE Transactions on Medical Imaging, vol. 41, no. 1, pp. 145–157, 2021.
- J. Zhang, X. He, L. Qing, F. Gao, and B. Wang, “BPGAN: Brain PET synthesis from MRI using generative adversarial network for multi-modal Alzheimer’s disease diagnosis,” Computer Methods and Programs in Biomedicine, vol. 217, p. 106676, 2022.
- F. Vega, A. Addeh, A. Ganesh, E. E. Smith, and M. E. MacDonald, “Image translation for estimating two-dimensional axial amyloid-beta PET from structural MRI,” Journal of Magnetic Resonance Imaging, vol. 59, no. 3, pp. 1021–1031, 2024.
- I. Goodfellow, “Nips 2016 tutorial: Generative adversarial networks,” arXiv preprint arXiv:1701.00160, 2016.
- F. Li, W. Huang, M. Luo, P. Zhang, and Y. Zha, “A new VAE-GAN model to synthesize arterial spin labeling images from structural MRI,” Displays, vol. 70, p. 102079, 2021.
- H. Yang, X. Lu, S.-H. Wang, Z. Lu, J. Yao, Y. Jiang, and P. Qian, “Synthesizing multi-contrast MR images via novel 3D conditional variational auto-encoding GAN,” Mobile Networks and Applications, vol. 26, pp. 415–424, 2021.
- J. Lucas, G. Tucker, R. B. Grosse, and M. Norouzi, “Don’t blame the ELBO! a linear VAE perspective on posterior collapse,” Advances in Neural Information Processing Systems, vol. 32, 2019.
- J. Sohl-Dickstein, E. Weiss, N. Maheswaranathan, and S. Ganguli, “Deep unsupervised learning using nonequilibrium thermodynamics,” in International Conference on Machine Learning. PMLR, 2015, pp. 2256–2265.
- J. Ho, A. Jain, and P. Abbeel, “Denoising diffusion probabilistic models,” Advances in Neural Information Processing Systems, vol. 33, pp. 6840–6851, 2020.
- P. Dhariwal and A. Nichol, “Diffusion models beat GANs on image synthesis,” Advances in Neural Information Processing Systems, vol. 34, pp. 8780–8794, 2021.
- H. Cao, C. Tan, Z. Gao, Y. Xu, G. Chen, P.-A. Heng, and S. Z. Li, “A survey on generative diffusion models,” IEEE Transactions on Knowledge and Data Engineering, 2024.
- A. Kazerouni, E. K. Aghdam, M. Heidari, R. Azad, M. Fayyaz, I. Hacihaliloglu, and D. Merhof, “Diffusion models in medical imaging: A comprehensive survey,” Medical Image Analysis, p. 102846, 2023.
- G. Chételat, J. Arbizu, H. Barthel, V. Garibotto, I. Law, S. Morbelli, E. van de Giessen, F. Agosta, F. Barkhof, D. J. Brooks et al., “Amyloid-PET and 18F-FDG-PET in the diagnostic investigation of Alzheimer’s disease and other dementias,” The Lancet Neurology, vol. 19, no. 11, pp. 951–962, 2020.
- M. W. Weiner, D. P. Veitch, P. S. Aisen, L. A. Beckett, N. J. Cairns, R. C. Green, D. Harvey, C. R. Jack, W. Jagust, E. Liu et al., “The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception,” Alzheimer’s & Dementia, vol. 9, no. 5, pp. e111–e194, 2013.
- R. J. Perrin, A. M. Fagan, and D. M. Holtzman, “Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease,” Nature, vol. 461, no. 7266, pp. 916–922, 2009.
- K. Walhovd, A. Fjell, A. Dale, L. McEvoy, J. Brewer, D. Karow, D. Salmon, and C. Fennema-Notestine, “Multi-modal imaging predicts memory performance in normal aging and cognitive decline,” Neurobiology of Aging, vol. 31, no. 7, pp. 1107–1121, 2010.
- C. R. Jack Jr, V. J. Lowe, M. L. Senjem, S. D. Weigand, B. J. Kemp, M. M. Shiung, D. S. Knopman, B. F. Boeve, W. E. Klunk, C. A. Mathis et al., “11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment,” Brain, vol. 131, no. 3, pp. 665–680, 2008.
- M. Abdelaziz, T. Wang, and A. Elazab, “Alzheimer’s disease diagnosis framework from incomplete multimodal data using convolutional neural networks,” Journal of Biomedical Informatics, vol. 121, p. 103863, 2021.
- K. Ritter, J. Schumacher, M. Weygandt, R. Buchert, C. Allefeld, and J.-D. Haynes, “Multimodal prediction of conversion to Alzheimer’s disease based on incomplete biomarkers,” Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, vol. 1, no. 2, pp. 206–215, 2015.
- L. Yuan, Y. Wang, P. M. Thompson, V. A. Narayan, and J. Ye, “Multi-source feature learning for joint analysis of incomplete multiple heterogeneous neuroimaging data,” NeuroImage, vol. 61, no. 3, pp. 622–632, 2012.
- S. Xiang, L. Yuan, W. Fan, Y. Wang, P. M. Thompson, J. Ye, A. D. N. Initiative et al., “Bi-level multi-source learning for heterogeneous block-wise missing data,” NeuroImage, vol. 102, pp. 192–206, 2014.
- T. Xie, C. Cao, Z. Cui, Y. Guo, C. Wu, X. Wang, Q. Li, Z. Hu, T. Sun, Z. Sang et al., “Synthesizing PET images from high-field and ultra-high-field MR images using joint diffusion attention model,” arXiv preprint arXiv:2305.03901, 2023.
- I. Goodfellow, J. Pouget-Abadie, M. Mirza, B. Xu, D. Warde-Farley, S. Ozair, A. Courville, and Y. Bengio, “Generative adversarial networks,” Communications of the ACM, vol. 63, no. 11, pp. 139–144, 2020.
- O. Ronneberger, P. Fischer, and T. Brox, “U-Net: Convolutional networks for biomedical image segmentation,” in Medical Image Computing and Computer-Assisted Intervention. Springer, 2015, pp. 234–241.
- D. P. Kingma and M. Welling, “Auto-encoding variational bayes,” in International Conference on Learning Representations, 2014.
- A. B. L. Larsen, S. K. Sonderby, H. Larochelle, and O. Winther, “Autoencoding beyond pixels using a learned similarity metric,” in International Conference on Machine Learning. PMLR, 2016, pp. 1558–1566.
- B. Dai and D. Wipf, “Diagnosing and enhancing VAE models,” in International Conference on Learning Representations, 2019.
- S. R. Bowman, L. Vilnis, O. Vinyals, A. Dai, R. Jozefowicz, and S. Bengio, “Generating sentences from a continuous space,” in Proceedings of the 20th SIGNLL Conference on Computational Natural Language Learning, S. Riezler and Y. Goldberg, Eds., Berlin, Germany, Aug. 2016, pp. 10–21.
- Y. Song, J. Sohl-Dickstein, D. P. Kingma, A. Kumar, S. Ermon, and B. Poole, “Score-based generative modeling through stochastic differential equations,” in International Conference on Learning Representations, 2021.
- Q. Lyu and G. Wang, “Conversion between CT and MRI images using diffusion and score-matching models,” arXiv preprint arXiv:2209.12104, 2022.
- Y. Gong, “Gradient domain diffusion models for image synthesis,” arXiv preprint arXiv:2309.01875, 2023.
- C. R. Jack Jr., M. A. Bernstein, N. C. Fox, P. Thompson, G. Alexander, D. Harvey, B. Borowski, P. J. Britson, J. L. Whitwell, C. Ward, A. M. Dale, J. P. Felmlee, J. L. Gunter, D. L. Hill, R. Killiany, N. Schuff, S. Fox-Bosetti, C. Lin, C. Studholme, C. S. DeCarli, G. Krueger, H. A. Ward, G. J. Metzger, K. T. Scott, R. Mallozzi, D. Blezek, J. Levy, J. P. Debbins, A. S. Fleisher, M. Albert, R. Green, G. Bartzokis, G. Glover, J. Mugler, and M. W. Weiner, “The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods,” Journal of Magnetic Resonance Imaging: An Official Journal of the International Society for Magnetic Resonance in Medicine, vol. 27, no. 4, pp. 685–691, 2008.
- A. Vaswani, N. Shazeer, N. Parmar, J. Uszkoreit, L. Jones, A. N. Gomez, L. Kaiser, and I. Polosukhin, “Attention is all you need,” Advances in Neural Information Processing Systems, vol. 30, 2017.
- M. J. Cardoso, W. Li, R. Brown, N. Ma, E. Kerfoot, Y. Wang, B. Murrey, A. Myronenko, C. Zhao, D. Yang et al., “Monai: An open-source framework for deep learning in healthcare,” arXiv preprint arXiv:2211.02701, 2022.
- S. Xiao, M. Lewis, D. Mellor, M. McCabe, L. Byrne, T. Wang, J. Wang, M. Zhu, Y. Cheng, C. Yang, and D. S, “The China longitudinal ageing study: Overview of the demographic, psychosocial and cognitive data of the Shanghai sample,” Journal of Mental Health, vol. 25, no. 2, pp. 131–136, 2016.
- K. A. Ellis, A. I. Bush, D. Darby, D. De Fazio, J. Foster, P. Hudson, N. T. Lautenschlager, N. Lenzo, R. N. Martins, P. Maruff et al., “The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: Methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer’s disease,” International Psychogeriatrics, vol. 21, no. 4, pp. 672–687, 2009.
- F. Jessen, R. E. Amariglio, M. Van Boxtel, M. Breteler, M. Ceccaldi, G. Chételat, B. Dubois, C. Dufouil, K. A. Ellis, W. M. Van Der Flier et al., “A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease,” Alzheimer’s & Dementia, vol. 10, no. 6, pp. 844–852, 2014.
- K. Abdulrab and R. Heun, “Subjective Memory Impairment. A review of its definitions indicates the need for a comprehensive set of standardised and validated criteria,” European Psychiatry, vol. 23, no. 5, pp. 321–330, 2008.
- P. S. Aisen, R. C. Petersen, M. Donohue, and M. W. Weiner, “Alzheimer’s disease neuroimaging initiative 2 clinical core: Progress and plans,” Alzheimer’s & Dementia, vol. 11, no. 7, pp. 734–739, 2015.
- Y. Pan, M. Liu, C. Lian, T. Zhou, Y. Xia, and D. Shen, “Synthesizing missing PET from MRI with cycle-consistent generative adversarial networks for Alzheimer’s disease diagnosis,” in Medical Image Computing and Computer Assisted Intervention. Springer, 2018, pp. 455–463.
- R. Rombach, A. Blattmann, D. Lorenz, P. Esser, and B. Ommer, “High-resolution image synthesis with latent diffusion models,” in Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition, 2022, pp. 10 684–10 695.
- P. S. Aisen, R. C. Petersen, M. C. Donohue, A. Gamst, R. Raman, R. G. Thomas, S. Walter, J. Q. Trojanowski, L. M. Shaw, L. A. Beckett, C. R. Jack Jr, W. Jagust, A. W. Toga, A. J. Saykin, J. C. Morris, R. C. Green, M. W. Weiner, and Alzheimer’s Disease Neuroimaging Initiative, “Clinical core of the Alzheimer’s Disease Neuroimaging Initiative: Progress and plans,” Alzheimer’s & Dementia, vol. 6, no. 3, pp. 239–246, 2010.
- J. C. Morris, “Clinical dementia rating: A reliable and valid diagnostic and staging measure for dementia of the Alzheimer type,” International Psychogeriatrics, vol. 9, no. S1, pp. 173–176, 1997.
- V. K. Shivamurthy, A. K. Tahari, C. Marcus, and R. M. Subramaniam, “Brain FDG PET and the diagnosis of dementia,” American Journal of Roentgenology, vol. 204, no. 1, pp. W76–W85, 2015.
- M. Dumba, S. Khan, N. Patel, L. Perry, P. Malhotra, R. Perry, K. Nijran, T. Barwick, K. Wallitt, and Z. Win, “Clinical 18F-FDG and amyloid brain positron emission tomography/CT in the investigation of cognitive impairment: Where are we now?” The British Journal of Radiology, vol. 92, no. 1101, p. 20181027, 2019.
- C. M. Clark, J. A. Schneider, B. J. Bedell, T. G. Beach, W. B. Bilker, M. A. Mintun, M. J. Pontecorvo, F. Hefti, A. P. Carpenter, M. L. Flitter et al., “Use of florbetapir-PET for imaging β𝛽\betaitalic_β-amyloid pathology,” JAMA, vol. 305, no. 3, pp. 275–283, 2011.
- J. Song, C. Meng, and S. Ermon, “Denoising diffusion implicit models,” in International Conference on Learning Representations, 2021.