Mathematical models for the diffusion magnetic resonance signal abnormality in patients with prion diseases

NeuroImage: Clinical

Daniel C. Alexander¹  Fabrizio Fasano²  Giuseppe Baselli³  Pierluigi Gambetti⁴  Veronica Redaelli⁵  Fabrizio Tagliavini⁵  Marina Grisoli⁶  Matteo Figini⁶  Alberto Bizzi⁷ 

[1] Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom;Department of Neuroscience, Università degli Studi di Parma, Parma, Italy;Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy;National Prion Disease Pathology Surveillance Center, Department of Pathology, Case Western Reserve University, Cleveland, OH, USA;Neuropathology, Fondazione IRCCS Istituto Neurologico, Parma, Italy;Neuroradiology, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, Milano, Italy;Neuroradiology, Humanitas Research Hospital IRCCS, Rozzano, Milano, Italy;

关键词: Diffusion MRI;    Biophysical models;    Creutzfeldt–Jakob disease;    Prion disease;    Spongiform degeneration;   

DOI  :  10.1016/j.nicl.2014.11.017

来源: DOAJ

【 摘 要 】

In clinical practice signal hyperintensity in the cortex and/or in the striatum on magnetic resonance (MR) diffusion-weighted images (DWIs) is a marker of sporadic Creutzfeldt–Jakob Disease (sCJD). MR diagnostic accuracy is greater than 90%, but the biophysical mechanisms underpinning the signal abnormality are unknown. The aim of this prospective study is to combine an advanced DWI protocol with new mathematical models of the microstructural changes occurring in prion disease patients to investigate the cause of MR signal alterations. This underpins the later development of more sensitive and specific image-based biomarkers. DWI data with a wide a range of echo times and diffusion weightings were acquired in 15 patients with suspected diagnosis of prion disease and in 4 healthy age-matched subjects. Clinical diagnosis of sCJD was made in nine patients, genetic CJD in one, rapidly progressive encephalopathy in three, and Gerstmann–Sträussler–Scheinker syndrome in two. Data were analysed with two bi-compartment models that represent different hypotheses about the histopathological alterations responsible for the DWI signal hyperintensity. A ROI-based analysis was performed in 13 grey matter areas located in affected and apparently unaffected regions from patients and healthy subjects. We provide for the first time non-invasive estimate of the restricted compartment radius, designed to reflect vacuole size, which is a key discriminator of sCJD subtypes. The estimated vacuole size in DWI hyperintense cortex was in the range between 3 and 10 µm that is compatible with neuropathology measurements. In DWI hyperintense grey matter of sCJD patients the two bi-compartment models outperform the classic mono-exponential ADC model. Both new models show that T2 relaxation times significantly increase, fast and slow diffusivities reduce, and the fraction of the compartment with slow/restricted diffusion increases compared to unaffected grey matter of patients and healthy subjects. Analysis of the raw DWI signal allows us to suggest the following acquisition parameters for optimized detection of CJD lesions: b = 3000 s/mm2 and TE = 103 ms. In conclusion, these results provide the first in vivo estimate of mean vacuole size, new insight on the mechanisms of DWI signal changes in prionopathies and open the way to designing an optimized acquisition protocol to improve early clinical diagnosis and subtyping of sCJD.

【 授权许可】

Unknown