6533b839fe1ef96bd12a647e

RESEARCH PRODUCT

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

Alberto BizziDaniel C. AlexanderPierluigi GambettiVeronica RedaelliFabrizio TagliaviniGiuseppe BaselliFabrizio FasanoMarina GrisoliMatteo Figini

subject

MalePathologysCJD sporadic Creutzfeldt–Jakob diseaseROI region of interestPrion diseasePrPSc prion protein scrapieElectroencephalographyFOV field of viewlcsh:RC346-429Prion DiseasesADC apparent diffusion coefficientTI inversion timeRPE rapidly progressive encephalopathyAged 80 and overTE echo timeBrain Mappingmedicine.diagnostic_testBrainRegular ArticleMiddle AgedBIC Bayesian information criterionTR repetition timemedicine.anatomical_structureNeurologylcsh:R858-859.7FemaleMPRAGE magnetization-prepared rapid acquisition gradient-echoAbnormalitySS-SE single shot spin-echoAdultmedicine.medical_specialtyCognitive NeuroscienceCreutzfeldt–Jakob diseaseCNR contrast to noise ratioEPI echo-planar imagingNeuropathologyPrPC prion protein cellularGrey matterSpongiform degenerationlcsh:Computer applications to medicine. Medical informaticsEEG electroencephalogramDiffusion MRINeuroimagingImage Interpretation Computer-AssistedmedicineHumansRadiology Nuclear Medicine and imaginglcsh:Neurology. Diseases of the nervous systemAgedCJD Creutzfeldt–Jakob diseaseGSS Gerstmann–Sträussler–Scheinker syndromebusiness.industryDWI diffusion weighted imagingDiffusion MRI; Biophysical models; Creutzfeldt-Jakob disease; Prion disease; Spongiform degenerationMagnetic resonance imagingModels TheoreticalHyperintensityCreutzfeldt-Jakob diseaseDiffusion Magnetic Resonance ImagingNeurology (clinical)businessBiophysical modelsDiffusion MRI

description

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.

10.1016/j.nicl.2014.11.017http://www.sciencedirect.com/science/article/pii/S2213158214001818