Large-scale longitudinal multi-site MRI brain morphometry studies are becoming increasingly crucial to characterize both normal and clinical population groups using fully automated segmentation ...tools. The test–retest reproducibility of morphometry data acquired across multiple scanning sessions, and for different MR vendors, is an important reliability indicator since it defines the sensitivity of a protocol to detect longitudinal effects in a consortium. There is very limited knowledge about how across-session reliability of morphometry estimates might be affected by different 3T MRI systems. Moreover, there is a need for optimal acquisition and analysis protocols in order to reduce sample sizes. A recent study has shown that the longitudinal FreeSurfer segmentation offers improved within session test–retest reproducibility relative to the cross-sectional segmentation at one 3T site using a nonstandard multi-echo MPRAGE sequence. In this study we implement a multi-site 3T MRI morphometry protocol based on vendor provided T1 structural sequences from different vendors (3D MPRAGE on Siemens and Philips, 3D IR-SPGR on GE) implemented in 8 sites located in 4 European countries. The protocols used mild acceleration factors (1.5–2) when possible. We acquired across-session test–retest structural data of a group of healthy elderly subjects (5 subjects per site) and compared the across-session reproducibility of two full-brain automated segmentation methods based on either longitudinal or cross-sectional FreeSurfer processing. The segmentations include cortical thickness, intracranial, ventricle and subcortical volumes. Reproducibility is evaluated as absolute changes relative to the mean (%), Dice coefficient for volume overlap and intraclass correlation coefficients across two sessions. We found that this acquisition and analysis protocol gives comparable reproducibility results to previous studies that used longer acquisitions without acceleration. We also show that the longitudinal processing is systematically more reliable across sites regardless of MRI system differences. The reproducibility errors of the longitudinal segmentations are on average approximately half of those obtained with the cross sectional analysis for all volume segmentations and for entorhinal cortical thickness. No significant differences in reliability are found between the segmentation methods for the other cortical thickness estimates. The average of two MPRAGE volumes acquired within each test–retest session did not systematically improve the across-session reproducibility of morphometry estimates. Our results extend those from previous studies that showed improved reliability of the longitudinal analysis at single sites and/or with non-standard acquisition methods. The multi-site acquisition and analysis protocol presented here is promising for clinical applications since it allows for smaller sample sizes per MRI site or shorter trials in studies evaluating the role of potential biomarkers to predict disease progression or treatment effects.
•We implemented a multi-site 3T MRI protocol for brain morphometry on 8EU sites.•We acquired across-session test-retest data on 40 healthy elderly subjects.•We calculated the reproducibility of cortical and volumetric FreeSurfer estimates.•Longitudinal segmentation was more reliable than cross-sectional on all sites.
New bifunctional and bimodal nanoparticles (NPs) have been elaborated and characterised. They are based on silica NPs that incorporate a silylated ruthenium tris‐bipyridine complex. The resulting ...suspension of amine‐modified NPs with diameters of 20 nm was post‐functionalised with a stable gadolinium ion complex. Interest in these NPs lies mainly in the confinement of optical and magnetic imaging agents (Ru and Gd complexes, respectively) within the NP volume. Their potential use as a bimodal probe (luminescence/magnetic resonance imaging) and theranostic agent (photodynamic therapy/imaging) is described. The biological potential of these NPs has been studied on HCT‐116 cells and microscopy and cytotoxicity results are given.
Dual action: Bifunctional and bimodal nanoparticles (NPs) based on silica NPs that incorporate ruthenium complex and grafted with gadolinium complex (see figure) have been developed for potential use as a bimodal probe (luminescence/magnetic resonance imaging) and theranostic agent (photodynamic therapy/imaging). The biological potential of these NPs has been studied on HCT‐116 cells and microscopy and cytotoxicity results are given.
Now that access of large domestic mammals to high-field MRI becomes more common, techniques initially implemented for human patients can be used for the structural and functional study of the brain ...of these animals. Among them, susceptibility-weighted imaging (SWI) is a recent technique obtained from gradient echo (GE) imaging that allow for an excellent anatomical tissue contrast and a non-invasive assessment of brain iron content. The goal of this study was to design an optimal GE SWI imaging protocol to be used in dogs undergoing an MRI examination of the brain in a 3-Tesla scanner. This imaging protocol was applied to
ex vivo
brains from four dogs. The imaging protocol was validated by visual inspection of the SWI images that provided a high anatomical detail, as demonstrated by their comparison with corresponding microscopic sections. As resolvable brain structures were labeled, this study is the first to provide an anatomic description of SWI images of the canine brain. Once validated in living animals, this GE SWI imaging protocol could be easily included in routine neuroimaging protocols to improve the diagnosis of various intracranial diseases of dogs, or be used in future comparative studies aiming at evaluating brain iron content in animals.
Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in ...healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2×2×2mm3, b=700s/mm2, 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test–retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test–retest reproducibility. White matter b0 SNR reproducibility was on average 7±1% with no significant MRI site effects. Whole brain analysis resulted in no significant test–retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2–4% range for FA and AD and 2–6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios.
•We implement a multi-site 3T MRI protocol for brain DTI on 10 EU sites.•We acquire across-session test–retest data on 50 healthy elderly subjects.•We use full brain TBSS and ROI analysis to calculate FA, MD, RD and AD.•Reproducibility errors are in the 2–6% range.•Reproducibility errors tended to be lower in sites with shorter acquisitions.
Over several decades, metal-doped quantum dots (QDs) with core–shell structure have been studied as dual probes: fluorescence and magnetic resonance imaging (MRI) probes (Dixit et al., Mater Lett ...63(30):2669–2671,
2009
). However, metal-doped nanoparticles, in which the majority of metal ions are close to the surface, can affect their efficacy as MRI contrast agents (CAs). In this context, herein the high potential of synthesized Mn-doped ZnS QDs via polyol method as imaging probe is demonstrated. The mean diameters of QDs were measured via transmission electron microscopy (TEM) and X-ray diffraction (XRD). Optical and magnetic properties of MnZnS nanoparticles were characterized using fluorescence spectroscopy and super quanducting interference devices magnetometer and electron paramagnetic resonance system, respectively. T1- and T2-weighted images of nanoparticles in aqueous solution were acquired from spin–echo sequences at 3 T. From TEM images and XRD spectra of the prepared nanoparticles, it is observed that the average diameter of particles does not significantly change with Mn dopant content (~1.6–1.9 nm). All three samples exhibit broad blue emission under UV light excitation. According to the MRI studies, MnZnS nanoparticles generate strong T1 contrast enhancement (bright T1-weighted images) at the low concentration (<0.1 mM). The MnZnS nanoparticles exhibit the high longitudinal (
r
1
) relaxivity that increases from 20.34 to 75.5 mM
−1
s
−1
with the Mn dopant contents varying between 10 and 30 %. Strong signal intensity on T1-weighted images and high
r
1
with
r
2
r
1
≈
1
can demonstrate the high potential of the synthesized Mn:ZnS nanoparticles, which can serve as an effective T1 CA.
•Common long-term memory defects after pediatric brain tumor affect school achievement•The hippocampi, the cerebellum and cerebellar-cortical networks play a role in several memory systems.•This ...study will provide long-term neuropsychological data about four different memory systems.•We will investigate the correlations between neuropsychological, neuroimaging and radiotherapy dose data.•Imaging will be structural (3DT1), microstructural (DTI), functional (rs-fMRI), vascular (ASL) and metabolic (spectroscopy).
Posterior fossa tumors represent two thirds of brain tumors in children. Although progress in treatment has improved survival rates over the past few years, long-term memory impairments in survivors are frequent and have an impact on academic achievement. The hippocampi, cerebellum and cerebellar-cortical networks play a role in several memory systems. They are affected not only by the location of the tumor itself and its surgical removal, but also by the supratentorial effects of complementary treatments, particularly radiotherapy. The IMPALA study will investigate the impact of irradiation doses on brain structures involved in memory, especially the hippocampi and cerebellum.
In this single-center prospective behavioral and neuro-imaging study, 90 participants will be enrolled in three groups. The first two groups will include patients who underwent surgery for a posterior fossa brain tumor in childhood, who are considered to be cured, and who completed treatment at least 5 years earlier, either with radiotherapy (aggressive brain tumor; Group 1) or without (low-grade brain tumor; Group 2). Group 3 will include control participants matched with Group 1 for age, sex, and handedness. All participants will perform an extensive battery of neuropsychological tests, including an assessment of the main memory systems, and undergo multimodal 3 T MRI. The irradiation dose to the different brain structures involved in memory will be collected from the initial radiotherapy dosimetry.
This study will provide long-term neuropsychological data about four different memory systems (working memory, episodic memory, semantic memory, and procedural memory) and the cognitive functions (attention, language, executive functions) that can interfere with them, in order to better characterize memory deficits among the survivors of brain tumors. We will investigate the correlations between neuropsychological and neuroimaging data on the structural (3DT1), microstructural (DTI), functional (rs-fMRI), vascular (ASL) and metabolic (spectroscopy) impact of the tumor and irradiation dose. This study will thus inform the setting of dose constraints to spare regions linked to the development of cognitive and memory functions.
ClinicalTrials.gov: NCT04324450, registered March 27, 2020, updated January 25th, 2021. Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04324450.
The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in ...multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults.
Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1–90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session.
Significant MRI site and vendor effects (p < .05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman’s r correlations >0.43, p < 1.39E-36). In particular, volumes larger than 200 mm3 (for amygdalar nuclei) and 300 mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε < 5% and DICE > 0.80).
Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.
•Differences in MRI site/vendor had a limited effect on volume reproducibility.•Differences in MRI site/vendor had an extensive effect on spatial accuracy.•Reliability is good for larger amygdalar and hippocampal structures.•Automated volumetry is reliable in multicenter MRI studies.
To date, limited data are available regarding the inter-site consistency of test–retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default ...Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0T using vendor-provided sequences. Each site scanned a group of 5 healthy elderly participants twice, at least a week apart. We evaluated inter-site differences and test–retest reproducibility of both temporal signal-to-noise ratio (tSNR) and functional connectivity measurements derived from: i) seed-based analysis (SBA) with seed in the posterior cingulate cortex (PCC), ii) group independent component analysis (ICA) separately for each site (site ICA), and iii) consortium ICA, with group ICA across the whole consortium. Despite protocol harmonization, significant and quantitatively important inter-site differences remained in the tSNR of resting-state fMRI data; these were plausibly driven by hardware and pulse sequence differences across scanners which could not be harmonized. Nevertheless, the tSNR test–retest reproducibility in the consortium was high (ICC=0.81). The DMN was consistently extracted across all sites and analysis methods. While significant inter-site differences in connectivity scores were found, there were no differences in the associated test–retest error. Overall, ICA measurements were more reliable than PCC-SBA, with site ICA showing higher reproducibility than consortium ICA. Across the DMN nodes, the PCC yielded the most reliable measurements (≈4% test–retest error, ICC=0.85), the medial frontal cortex the least reliable (≈12%, ICC=0.82) and the lateral parietal cortices were in between (site ICA). Altogether these findings support usage of harmonized multisite studies of resting-state functional connectivity to characterize longitudinal effects in studies that assess disease progression and treatment response.
•We implement a multi-site 3T MRI protocol for resting state fMRI in 13 sites.•We acquire across-session test–retest (TRT) data on 64 healthy elderly participants.•Despite harmonization strong phantom and brain tSNR differences remain across sites.•TRT error of regional DMN functional connectivity is consistent across sites.•ICA yields more reliable DMN connectivity measurements relative to SBA.