Carlo Cavaliere

Relationship between simultaneously acquired resting-state regional cerebral glucose metabolism and functional MRI: A PET/MR hybrid scanner study

Recently introduced hybrid PET/MR scanners provide the opportunity to measure simultaneously, and in direct spatial correspondence, both metabolic demand and functional activity of the brain, hence capturing complementary information on the brains physiological state. Here we exploited PET/MR simultaneous imaging to explore the relationship between the metabolic information provided by resting-state fluorodeoxyglucose-PET (FDG-PET) and fMRI (rs-fMRI) in neurologically healthy subjects. Regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and degree of centrality (DC) maps were generated from the rs-fMRI data in 23 subjects, and voxel-wise comparison to glucose uptake distribution provided by simultaneously acquired FDG-PET was performed. The mutual relationships among each couple of these four metrics were explored in terms of similarity, both of spatial distribution across the brain and the whole group, and voxel-wise across subjects, taking into account partial volume effects by adjusting for grey matter (GM) volume. Although a significant correlation between the spatial distribution of glucose uptake and rs-fMRI derived metrics was present, only a limited percentage of GM voxels correlated with PET across subjects. Moreover, the correlation between the spatial distributions of PET and rs-fMRI-derived metrics is spatially heterogeneous across both anatomic regions and functional networks, with lowest correlation strength in the limbic network (Spearman rho around -0.11 for DC), and strongest correlation for the default-mode network (up to 0.89 for ReHo and 0.86 for fALFF). Overall, ReHo and fALFF provided significantly higher correlation coefficients with PET (p=10(-8) and 10(-7), respectively) as compared to DC, while no significant differences were present between ReHo and fALFF. Local GM volume variations introduced a limited overestimation of the rs-fMRI to FDG correlation between the modalities under investigation through partial volume effects. These novel results provide the basis for future studies of alterations of the coupling between brain metabolism and functional connectivity in pathologic conditions.

Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study.

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.

Simultaneous PET/MR head–neck cancer imaging: Preliminary clinical experience and multiparametric evaluation

PURPOSEnTo evaluate the role of simultaneous hybrid PET/MR imaging and to correlate metabolic PET data with morpho-functional parameters derived by MRI in patients with head-neck cancer.nnnMETHODSnForty-four patients, with histologically confirmed head and neck malignancy (22 primary tumors and 22 follow-up) were studied. Patients initially received a clinical exam and endoscopy with direct biopsy. Next patients underwent whole body PET/CT followed by PET/MR of the head/neck region. PET and MRI studies were separately evaluated by two blinded groups (both included one radiologist and one nuclear physician) in order to define the presence or absence of lesions/recurrences. Regions of interest (ROIs) analysis was conducted on the primary lesion at the level of maximum size on metabolic (SUV and MTV), diffusion (ADC) and perfusion (K(trans), Ve, kep and iAUC) parameters.nnnRESULTSnPET/MR examinations were successfully performed on all 44 patients. Agreement between the two blinded groups was found in anatomic allocation of lesions by PET/MR (Primary tumors: Cohens kappa 0.93;nnnFOLLOW-UPnCohens kappa 0.89). There was a significant correlation between CT-SUV measures and MR (e.g., CT-SUV VOI vs.nnnMR-SUV VOInρ=0.97, p<0.001 for the entire sample). There was also significant positive correlations between the ROI area, SUV measures, and the metabolic parameters (SUV and MTV) obtained during both PET/CT and PET/MR. A significant negative correlation was observed between ADC and K(trans) values in the primary tumors. In addition, a significant negative correlation existed between MR SUV and ADC in recurrent tumors.nnnCONCLUSIONnOur study demonstrates the feasibility of PET/MR imaging for primary tumors and recurrent tumors evaluations of head/neck malignant lesions. When assessing HNC, PET/MR allows simultaneous collection of multiparametric metabolic and functional data. This technique therefore allows for a more complete characterization of malignant lesions.

Longitudinal reproducibility of automatically segmented hippocampal subfields: A multisite European 3T study on healthy elderly.

Recently, there has been an increased interest in the use of automatically segmented subfields of the human hippocampal formation derived from magnetic resonance imaging (MRI). However, little is known about the test‐retest reproducibility of such measures, particularly in the context of multisite studies. Here, we report the reproducibility of automated Freesurfer hippocampal subfields segmentations in 65 healthy elderly enrolled in a consortium of 13 3T MRI sites (five subjects per site). Participants were scanned in two sessions (test and retest) at least one week apart. Each session included two anatomical 3D T1 MRI acquisitions harmonized in the consortium. We evaluated the test‐retest reproducibility of subfields segmentation (i) to assess the effects of averaging two within‐session T1 images and (ii) to compare subfields with whole hippocampus volume and spatial reliability. We found that within‐session averaging of two T1 images significantly improved the reproducibility of all hippocampal subfields but not that of the whole hippocampus. Volumetric and spatial reproducibility across MRI sites were very good for the whole hippocampus, CA2‐3, CA4‐dentate gyrus (DG), subiculum (reproducibility error∼2% and DICEu2009>u20090.90), good for CA1 and presubiculum (reproducibility error ∼ 5% and DICE ∼ 0.90), and poorer for fimbria and hippocampal fissure (reproducibility error ∼ 15% and DICEu2009<u20090.80). Spearmans correlations confirmed that test‐retest reproducibility improved with volume size. Despite considerable differences of MRI scanner configurations, we found consistent hippocampal subfields volumes estimation. CA2‐3, CA4‐DG, and sub‐CA1 (subiculum, presubiculum, and CA1 pooled together) gave test‐retest reproducibility similar to the whole hippocampus. Our findings suggest that the larger hippocampal subfields volume may be reliable longitudinal markers in multisite studies. Hum Brain Mapp 36:3516–3527, 2015.

Hybrid PET/MR Imaging and Brain Connectivity.

In recent years, brain connectivity is gaining ever-increasing interest from the interdisciplinary research community. The study of brain connectivity is characterized by a multifaceted approach providing both structural and functional evidence of the relationship between cerebral regions at different scales. Although magnetic resonance (MR) is the most established imaging modality for investigating connectivity in vivo, the recent advent of hybrid positron emission tomography (PET)/MR scanners paved the way for more comprehensive investigation of brain organization and physiology. Due to the high sensitivity and biochemical specificity of radiotracers, combining MR with PET imaging may enrich our ability to investigate connectivity by introducing the concept of metabolic connectivity and cometomics and promoting new insights on the physiological and molecular bases underlying high-level neural organization. This review aims to describe and summarize the main methods of analysis of brain connectivity employed in MR imaging and nuclear medicine. Moreover, it will discuss practical aspects and state-of-the-art techniques for exploiting hybrid PET/MR imaging to investigate the relationship of physiological processes and brain connectivity.

Radiogenomic Analysis of Oncological Data: A Technical Survey

In the last few years, biomedical research has been boosted by the technological development of analytical instrumentation generating a large volume of data. Such information has increased in complexity from basic (i.e., blood samples) to extensive sets encompassing many aspects of a subject phenotype, and now rapidly extending into genetic and, more recently, radiomic information. Radiogenomics integrates both aspects, investigating the relationship between imaging features and gene expression. From a methodological point of view, radiogenomics takes advantage of non-conventional data analysis techniques that reveal meaningful information for decision-support in cancer diagnosis and treatment. This survey is aimed to review the state-of-the-art techniques employed in radiomics and genomics with special focus on analysis methods based on molecular and multimodal probes. The impact of single and combined techniques will be discussed in light of their suitability in correlation and predictive studies of specific oncologic diseases.

Free water elimination improves test–retest reproducibility of diffusion tensor imaging indices in the brain: A longitudinal multisite study of healthy elderly subjects

Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test–retest reproducibility. This study compares a bi‐tensor model for FWE with DTI by extending a previous longitudinal‐reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55–80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white‐matter regions of the JHU‐ICBM‐DTI‐81 white‐matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12–26, 2017.

Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients

Transcranial direct current stimulation (tDCS) is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS) patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions exist, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI) of 16 sub-acute and chronic MCS patients (6 tDCS responders) who successively received a single left dorsolateral prefrontal cortex (DLPFC) tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network (ECN) and default-mode network (DMN) was performed. tDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders (NR) MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus. Our findings suggest that a prior high connectivity with regions belonging to ECN can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS.

Diffusion tensor imaging and white matter abnormalities in patients with disorders of consciousness.

Progress in neuroimaging has yielded new powerful tools which, potentially, can be applied to clinical populations, improve the diagnosis of neurological disorders and predict outcome. At present, the diagnosis of consciousness disorders is limited to subjective assessment and objective measurements of behavior, with an emerging role for neuroimaging techniques. In this review we focus on white matter alterations measured using Diffusion Tensor Imaging on patients with consciousness disorders, examining the most common diffusion imaging acquisition protocols and considering the main issues related to diffusion imaging analyses. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps and the potential role of neuroimaging in understanding the pathogenesis and clinical features of disorders of consciousness.

Short parietal lobe connections of the human and monkey brain

The parietal lobe has a unique place in the human brain. Anatomically, it is at the crossroad between the frontal, occipital, and temporal lobes, thus providing a middle ground for multimodal sensory integration. Functionally, it supports higher cognitive functions that are characteristic of the human species, such as mathematical cognition, semantic and pragmatic aspects of language, and abstract thinking. Despite its importance, a comprehensive comparison of human and simian intraparietal networks is missing. In this study, we used diffusion imaging tractography to reconstruct the major intralobar parietal tracts in twenty-one datasets acquired inxa0vivo from healthy human subjects and eleven exxa0vivo datasets from five vervet and six macaque monkeys. Three regions of interest (postcentral gyrus, superior parietal lobule and inferior parietal lobule) were used to identify the tracts. Surface projections were reconstructed for both species and results compared to identify similarities or differences in tract anatomy (i.e., trajectories and cortical projections). In addition, post-mortem dissections were performed in a human brain. The largest tract identified in both human and monkey brains is a vertical pathway between the superior and inferior parietal lobules. This tract can be divided into an anterior (supramarginal gyrus) and a posterior (angular gyrus) component in both humans and monkey brains. The second prominent intraparietal tract connects the postcentral gyrus to both supramarginal and angular gyri of the inferior parietal lobule in humans but only to the supramarginal gyrus in the monkey brain. The third tract connects the postcentral gyrus to the anterior region of the superior parietal lobule and is more prominent in monkeys compared to humans. Finally, short U-shaped fibres in the medial and lateral aspects of the parietal lobe were identified in both species. A tract connecting the medial parietal cortex to the lateral inferior parietal cortex was observed in the monkey brain only. Our findings suggest a consistent pattern of intralobar parietal connections between humans and monkeys with some differences for those areas that have cytoarchitectonically distinct features in humans. The overall pattern of intraparietal connectivity supports the special role of the inferior parietal lobule in cognitive functions characteristic of humans.