Efstratios Karavasilis

Fiber tracking: A qualitative and quantitative comparison between four different software tools on the reconstruction of major white matter tracts

Purpose Diffusion tensor imaging (DTI) enables in vivo reconstruction of white matter (WM) pathways. Considering the emergence of numerous models and fiber tracking techniques, we herein aimed to compare, both quantitatively and qualitatively, the fiber tracking results of four DTI software (Brainance, Philips FiberTrak, DSI Studio, NordicICE) on the reconstruction of representative WM tracts. Materials and methods Ten healthy participants underwent 30-directional diffusion tensor imaging on a 3T-Philips Achieva TX MR-scanner. All data were analyzed by two independent sites of experienced raters with the aforementioned software and the following WM tracts were reconstructed: corticospinal tract (CST); forceps major (Fmajor); forceps minor (Fminor); cingulum bundle (CB); superior longitudinal fasciculus (SLF); inferior fronto-occipital fasciculus (IFOF). Visual inspection of the resulted tracts and statistical analysis (inter-rater and betweensoftware agreement; paired t-test) on fractional anisotropy (FA), axial and radial diffusivity (Daxial, Dradial) were applied for qualitative and quantitative evaluation of DTI software results. Results Qualitative evaluation of the extracted tracts confirmed anatomical landmarks at least for the core part of each tract, even though differences in the number of fibers extracted and the whole tract were evident, especially for the CST, Fmajor, Fminor and SLF. Descriptive values did not deviate from the expected range of values for healthy adult population. Substantial inter-rater agreement (intraclass correlation coefficient [ICC], Bland-Altman analysis) was found for all tracts (ICC; FA: 0.839–0.989, Daxial: 0.704–0.991, Dradial: 0.972–0.993). Low agreement for FA, Daxial and Dradial (ICC; Bland-Altman analysis) and significant paired t-test differences (p < 0.05) were detected regarding between-software agreement. Conclusions Qualitative comparison of four different DTI software in addition to substantial inter-rater but poor between-software agreement highlight the differences on existing fiber tracking methodologies and several particularities of each WM tract, further supporting the need for further study in both clinical and research settings.

Uncinate fasciculus microstructure and verbal episodic memory in amyotrophic lateral sclerosis: a diffusion tensor imaging and neuropsychological study

The present study evaluates the integrity of uncinate fasciculus (UF) and the association between UF microstructure and verbal episodic memory (as one of the cognitive functions linked to UF) in non-demented patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). We studied 21 patients with ALS and 11 healthy, demographically-comparable volunteers. Fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity were the DTI metrics examined. Episodic memory was evaluated with Babcock Story Recall Test and Rey Auditory Verbal Learning Test (RAVLT) for patients; measures of immediate and delayed recall and retention for both tests and sum of words recalled through five learning trials for RAVLT were considered. Patients with ALS showed significant bilateral reduction of axial diffusivity in the UF as compared to controls. Furthermore, there were several significant relations between various DTI metrics (mostly in left hemisphere) and memory measures (specifically for the RAVLT). UF microstructural changes may contribute to ALS-related memory impairment, with word-list learning performance relying more upon the integrity of frontal and temporal connections than memory components associated with story recall.

Evaluating cognitive models of visual word recognition using fMRI: Effects of lexical and sublexical variables

In this study predictions of the dual-route cascaded (DRC) model of word reading were tested using fMRI. Specifically, patterns of co-localization were investigated: (a) between pseudoword length effects and a pseudowords vs. fixation contrast, to reveal the sublexical grapho-phonemic conversion (GPC) system; and (b) between word frequency effects and a words vs. pseudowords contrast, to reveal the orthographic and phonological lexicon. Forty four native speakers of Greek were scanned at 3T in an event-related lexical decision task with three event types: (a) 150 words in which frequency, length, bigram and syllable frequency, neighborhood, and orthographic consistency were decorrelated; (b) 150 matched pseudowords; and (c) fixation. Whole-brain analysis failed to reveal the predicted co-localizations. Further analysis with participant-specific regions of interest defined within masks from the group contrasts revealed length effects in left inferior parietal cortex and frequency effects in the left middle temporal gyrus. These findings could be interpreted as partially consistent with the existence of the GPC system and phonological lexicon of the model, respectively. However, there was no evidence in support of an orthographic lexicon, weakening overall support for the model. The results are discussed with respect to the prospect of using neuroimaging in cognitive model evaluation.

Evaluation of organ and effective doses during paediatric barium meal examinations using PCXMC 2.0 Monte Carlo code

Radiation protection and estimation of the radiological risk in paediatric radiology is essential due to childrens significant radiosensitivity and their greater overall health risk. The purpose of this study was to estimate the organ and effective doses of paediatric patients undergoing barium meal (BM) examinations and also to evaluate the assessment of radiation Risk of Exposure Induced cancer Death (REID) to paediatric patients undergoing BM examinations. During the BM studies, fluoroscopy and multiple radiographs are involved. Since direct measurements of the dose in each organ are very difficult if possible at all, clinical measurements of dose-area products (DAPs) and the PCXMC 2.0 Monte Carlo code were involved. In clinical measurements, DAPs were assessed during examination of 51 patients undergoing BM examinations, separated almost equally in three age categories, neonatal, 1- and 5-y old. Organs receiving the highest amounts of radiation during BM examinations were as follows: the stomach (10.4, 10.2 and 11.1 mGy), the gall bladder (7.1, 5.8 and 5.2 mGy) and the spleen (7.5, 8.2 and 4.3 mGy). The three values in the brackets correspond to neonatal, 1- and 5-y-old patients, respectively. For all ages, the main contributors to the total organ and effective doses are the fluoroscopy projections. The average DAP values and absorbed doses to patient were higher for the left lateral projections. The REID was calculated for boys (4.8 × 10(-2), 3.0 × 10(-2) and 2.0 × 10(-2) %) for neonatal, 1- and 5-y old patients, respectively. The corresponding values for girl patients were calculated (12.1 × 10(-2), 5.5 × 10(-2) and 3.4 × 10(-2) %).

Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques

Abstract Objective: Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS). Methods: We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms. Results: In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold). Conclusions: PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.

The Clinical and Radiological Spectrum of Hippocampal Pathology in Amyotrophic Lateral Sclerosis

Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence from neuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely.

A specific pattern of gray matter atrophy in Alzheimer’s disease with depression

Considering the high incidence of depressive symptoms in Alzheimer’s disease (AD), we conducted a large-sample study to investigate the pattern of gray matter (GM) abnormalities that differentiates depressive from non-depressive AD patients. We included 201 AD patients who underwent MRI assessment and categorized them into depressive and non-depressive subgroups based on the Geriatric Depression Scale (GDS; cut-off score: ≤9). We performed whole-brain voxel-based morphometry analysis in 173 patients after MRI quality control and used between-group comparisons and regression analysis models to analyze the volumetric data controlling for nuisance variables. Depressive AD patients had extensive GM volume loss mainly in the paracentral region, specifically in post- and pre-central gyrus, supplementary motor areas and thalamus compared to non-depressive patients. Similar findings were obtained for the group of 173 patients using regression analysis and GDS score as predictor variable. We provided the first clear demonstration of a unique pattern of GM atrophy that characterizes AD patients with depression which is consistent with regions implicated in the phenomenon of psychomotor retardation that characterizes depression.

Verbal and Figural Fluency in Temporal Lobe Epilepsy: Does Hippocampal Sclerosis Affect Performance?

Background and Objectives: Clinicians commonly use verbal and nonverbal measures to test fluency in patients with epilepsy, either during routine cognitive assessment or as part of pre- and postsurgical evaluation. We hypothesized that patients with mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis would perform worse than patients with lateral TLE in both verbal and design fluency. Methods: We assessed semantic, phonemic, and nonverbal fluency in 49 patients with TLE: 31 with lateral TLE and 18 with mesial TLE plus hippocampal sclerosis. We also gave non-fluency cognitive measures: psychomotor speed, attentional set shifting, selective attention, abstract reasoning, verbal and visual episodic memory, and incidental memory. Results: Patients with mesial TLE performed significantly worse on figural fluency than patients with lateral TLE. Even though group differences on verbal fluency measures were not significant, the patients with mesial TLE had a pattern of poorer performance. The patients with mesial TLE scored significantly worse on measures of selective attention, verbal episodic memory, and incidental memory. Conclusions: Our study underlines differences in cognitive function between patients with mesial and lateral TLE, particularly in figural fluency. Although we cannot directly assess the role of the hippocampus in cognitive aspects of creative and divergent thinking related to figural fluency, the cognitive discrepancies between these two TLE groups could be ascribed to the mesial TLE hippocampal pathology shown in our study and addressed in the literature on hippocampal involvement in divergent thinking. Our findings could benefit cognitive rehabilitation programs tailored to the needs of patients with TLE.

Ipsilateral and contralateral cerebro-cerebellar white matter connections: A diffusion tensor imaging study in healthy adults

BACKGROUND AND PURPOSE The cerebellum has a pivotal role in regulating human behavior; yet whether this function is mediated only through contralateral cerebro-cerebellar pathways is under-investigated. Thus, we examined feed-backward and feed-forward ipsilateral and contralateral cerebro-cerebellar connections using a detereministic diffusion tensor imaging (DTI) algorithm, the robustness of which was also estimated using phantom DTI data. MATERIALS AND METHODS Fifty-one healthy controls (22-60 years old; 15 males/36 females) were scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of-interest (ROI) method was applied for the reconstruction of the ipsilateral and contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto-cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally using the Brainance DTI Suite. A realistic diffusion MR phantom was used to evaluate the fiber tracking methodology for 16 fibers containing crossing, kissing, splitting and bending configurations. RESULTS Both contralateral and ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully reconstructed; the contralateral DRTC tract was not reconstructed in all subjects. Also, the TPC tract was not reproduced in several subjects mostly regarding the contralateral connection. Descriptive DTI measures (number of fibers, fractional anisotropy, radial and axial diffusivity) are presented for each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16 fibers that almost perfectly matched the 16 ground truth fibers. CONCLUSIONS We identified ipsilateral and contralateral connections using a clinically applicable DTI sequence, a robust deterministic algorithm and an unbiased methodology, which can be applied in daily practice in different brain pathologies.

X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association

Objective X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, a gap junction protein expressed in Schwann cells, but also found in oligodendrocytes. Four patients with CMTX developing central nervous system (CNS) demyelination compatible with multiple sclerosis (MS) have been individually published. We presently sought to systematically investigate the relationship between CMTX and MS. Methods Over 20 years, 70 consecutive patients (36 men) with GJB1 mutations were identified at our Neurogenetics Unit, Athens, Greece, and assessed for clinical features suggestive of MS. Additionally, 18 patients with CMTX without CNS symptoms and 18 matched controls underwent brain MRI to investigate incidental findings. Serum from patients with CMTX and MS was tested for CNS immunoreactivity. Results We identified three patients with CMTX who developed clinical features suggestive of inflammatory CNS demyelination fulfilling MS diagnostic criteria. The resulting 20-year MS incidence (4.3%) differed significantly from the highest background 20-year MS incidence ever reported from Greece (p=0.00039). The search for incidental brain MRI findings identified two CMTX cases (11%) with lesions suggestive of focal demyelination compared with 0 control. Moreover, 10 cases in the CMTX cohort had hyperintensity in the splenium of the corpus callosum compared with 0 control (p=0.0002). No specific CNS-reactive humoral factors were identified in patients with CMTX and MS. Conclusions We have demonstrated a higher than expected frequency of MS in patients with CMTX and identified incidental focal demyelinating lesions on brain MRI in patients with CMTX without CNS symptoms. This provides circumstantial evidence for GJB1 mutations acting as a possible MS risk factor.