Alberto Bizzi, MD


Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

Grant Year: 




A large phenotypic variability in clinical presentation, brain lesion distribution, disease evolution and progression has led to the identification of several subtypes of prion diseases. This heterogeneity complicates early clinical diagnosis, prognosis, treatment, and design and testing of new drugs. Brain Magnetic Resonance Imaging (MRI) is the test of choice for the early diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), because it is a widely available clinical diagnostic test with a very high diagnostic sensitivity (94%) and specificity (98%)[1]. Currently, the sCJD subtype can be preliminary diagnosed with MRI [2] but definitely diagnosed only by tissue examination. We have recently shown with diffusion-weighted MRI that prion lesions begin and propagate in the brain following trajectories that are specific to the sCJD subtypes [3].

In this new project we have two aims:



  • to characterize sCJD patient subgroups as defined by different trajectories of prion lesion propagation in the brain based on MRI. The identification of these subgroups with different trajectories would allow to determine the disease stage and to predict the disease evolution of any new patient.
  • to investigate the mechanism underpinning the propagation of prion diseases in the brain. We will test whether lesion propagation affects primarily brain hubs or follows major anatomical connections between affected brain regions.

We will apply novel and powerful mathematical and computational models such as SuStaIn [4] to the largest database of brain MRI of more than 700 patients with autopsy confirmed diagnosis of CJD, collected by the National Prion Disease Pathology Surveillance Center (Cleveland, OH). We expect that the results of this project will have an impact on early and accurate diagnosis of sCJD and on clinical trials testing new drugs, which will likely depend and might need to be tailored to patient-specific characteristics.

[1] Bizzi et al. (2020) Evaluation of a New Criterion for Detecting Prion Disease With Diffusion Magnetic Resonance Imaging. JAMA Neurology 77(9):1141–1149.
[2] Bizzi et al. (2020) Subtype Diagnosis of Sporadic Creutzfeldt–Jakob Disease with Diffusion Magnetic Resonance Imaging. Annals of Neurology. Published online December 3, 2020.
[3] Pascuzzo et al. (2020) Prion propagation estimated from brain diffusion MRI is subtype dependent in sporadic Creutzfeldt–Jakob disease. Acta Neuropathologica 140:169–181.
[4] Young et al. (2018) Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference. Nature Communications 9, 4273.

About the Researcher:

Alberto Bizzi, MD
Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

Alberto Bizzi, M.D., is Board Certified in Radiology and Neurology. He completed a residency in Radiology and a fellowship in Neuroradiology at the Johns Hopkins University in Baltimore, MD, USA. Since 1997 he holds a tenure position at the Fondazione IRCCS Istituto Neurologico Besta in Milan. He holds a professorship appointment with the University of Milan to teach Neuroradiology to medical students and radiology residents.

Dr. Bizzi was the leader of the Work Package dedicated to prion diseases within the EuroPOND project from 2016 to 2020, funded by the European Commission (Horizon 2020 programme), aiming to develop new computational tools for understanding progression of neurological diseases. The main focus of his research in prion disease is the application of diffusion MRI to diagnose subtypes of sCJD and understand which histopathologic lesions are responsible for the signal abnormalities that are so typical of prion disease. He has been serving as a consultant to the National Prion Disease Surveillance Center (NPDSC) in Cleveland since 2008. At the ISMRM-ESMRMB Joint Annual Meeting in Berlin 2007 he received the Outstanding Teaching Award for the lecture "Diffusion Imaging and Pathological Correlation in Prion Diseases". Dr. Bizzi has been invited to give lectures and he has attended several meetings of the CJD Foundation. He is an enthusiastic supporter of this unique meeting that annually gathers clinicians, researchers, and families affected by prion disease.

Since his early training at the National Institute of Health and Johns Hopkins University, he has enjoyed working closely with scientists, MR physicists and neuropathologists. Dr. Bizzi believes that a close collaboration and effective communication between scientists, physicists, mathematicians and clinicians is instrumental to accelerate translation of scientific discoveries into real therapies for personalised patient care.

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