Langerhans cell histiocytosis: unusual dorsal spine localization in an adult male.

This case report describes the clinical, imaging, and pathological features of a case of Langerhans cell histiocytosis affecting a patient suffering from chronic thoracic spine pain. Spinal localizations of Langerhans cell histiocytosis have been rarely described and they are usually characterized by involvement of vertebral bodies with osteolytic lesions. Our case presented with several unusual features that delayed the diagnosis, including the age of patient and the involvement of left T10 costovertebral junction with relative sparing of vertebral body and costal bone. The clues for diagnosis were represented by increased signal intensity both on T 2W fat-saturated and T 1W images after administration of gadolinium. The diagnosis was finally confirmed by means of percutaneous biopsy with subsequent histological/immunohistochemical study.

Degenerative spine disease: Italian position paper on acquisition, interpretation and reporting of Magnetic Resonance Imaging.

OBJECTIVE: To promote a better radiological interpretation of spine degeneration, a consistent standardization of the acquisition, interpretation and description of Magnetic Resonance Imaging (MRI) l findings. MATERIALS AND METHODS: In order to achieve this objective, a consensus among experts in imaging of degenerative spine disease (DSD) from Italian radiological societies (SIRM-Italian Society of Radiology, AINR-Italian Association of Neuroradiology) was achieved. The representatives of the Italian inter-societal working group examined the literature produced by European/American task forces on optimizing the study sequences, classification of degenerative disc changes, spondylo-arthrosis, osteochondrosis, synovial and ligament pathologies of the spinal column, and on canal and foraminal stenosis. The document-resulted from the consensus between experts-was then presented to the scientific societies of Neurosurgery (SINCH) and Orthopedics and Traumatology (SIOT) for their approval. RESULTS: This position paper presents a proposal for an optimized MRI protocol for studying DSD and provides a glossary of terms related to this pathology and indications on their use. The international terminological recommendations have been translated and adapted to the Italian language and clinical practice and clinical cases have been used to illustrate some of the main classifications. CONCLUSIONS: This revision of international DSD guidelines/recommendations and consensus made it possible to (1) update the nomenclature to international standards and (2) harmonize the MRI protocol and description of radiological findings, adapting both (1, 2) to the Italian context. With this position paper we intend to contribute to an improvement of the communication among doctors and between physicians and their patients as well as the quality of the radiological reports.

Magnetic Resonance Spectroscopy in Adolescent Cannabis Users: Metabolites in the Anterior Cingulate Cortex Reflects Individual Differences in Personality Traits and can Affect Rehabilitation Compliance.

INTRODUCTION: The anterior cingulate cortex (ACC) has shown to play a role in impulsivity, fear, and anxiety. Considering, its high glutamate receptor density, it was chosen as a region of interest to investigate the role of glutamate transmission in drug dependance. We investigated the correlations between personality trait scores and glutamate-to-glutamine (Glx) ratio concentrations in the ACC in order to evaluate if (1) personality traits may increase the probability of drug use and (2) drug use can modify cerebral metabolic pattern contributing to addictive behaviors. MATERIALS AND METHODS: Glx ratio concentrations in the ACC region were measured with high-resolution multivoxel proton magnetic resonance spectroscopy (1H-MRS). Personality traits were evaluated utilizing Cloninger's TCI-revised test. Bivariate correlations between personality scores of 28 teens cannabis users (males, mean age = 18.54 ± 2.80) were evaluated. RESULTS: In the ACC, we observed negative correlation between GG concentrations (r = -0.44, P = 0.05) and co-operativeness values (CO), choline (cho), and novelty seeking (NS) values (r = -0,45, P = 0.05). Low levels of glutamate and high levels of cho in the ACC were closely related to the CO and NS personality traits. CONCLUSIONS: Metabolic and personality patterns seems to be related to the risk of substance predisposition in adolescents. Our data contribute a possible support to the "top-down" control of the ACC on brain metabolism, due to the particular cerebral metabolic pattern found in "drug-using" adolescents.

Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors.

BACKGROUND: 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. METHODS: 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. RESULTS: Significant MRI site and vendor effects (p â€‹< â€‹.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 â€‹< â€‹1.39E-36). In particular, volumes larger than 200 â€‹mm3 (for amygdalar nuclei) and 300 â€‹mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε â€‹< â€‹5% and DICE â€‹> â€‹0.80). CONCLUSION: 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.

Identification of bone marrow edema of the ankle: diagnostic accuracy of dual-energy CT in comparison with MRI.

OBJECTIVE: To evaluate the diagnostic accuracy of dual-energy computed tomography (DECT) to identify bone marrow edema (BME) of the ankle. METHODS: This prospective institutional review board approved study included 40 consecutive patients (29 males and 11 females; mean age of 32.3 years) studied with DECT (80 kV and tin filter 150 kV) and MRI within 10 days. DECT data were post-processed for generating non-calcium images of the ankle. Two radiologists evaluated the presence of BME on color-coded maps. Diagnostic accuracy values for diagnosing BME were calculated for DECT maps (qualitative assessment) and for CT numbers (quantitative assessment) by using receiver operator curves and area under the curve (AUC), using MRI as the gold standard. Interobserver and intraobserver agreements were calculated with k-statistics. A p < 0.05 was considered statistically significant. RESULTS: DECT depicted BME in 23/25 patients (92.0%). The sensitivity, specificity, PPV and NPV, and accuracy achieved by evaluating the DECT images were 92.0, 86.6, 92.0, 84.6, and 90.0%, for reader 1 and 88.0, 86.6, 91.6, 78.6, and 87.5, for reader 2, respectively. The interobserver and intraobsever agreements were near perfect (k = 0.87 and k = 0.83, respectively). DECT numbers were significantly different between positive (mean - 12.6 ± 29.6 HU) and negative cases (mean - 64.2 ± 34.5 HU) with a p value < 0.001. By using - 20HU cutoff to identify BME (AUC of 0.896.), the sensitivity, specificity, PPV and NPV, and accuracy of the quantitative analysis were 88.0, 92.6, 95.7, 92.6, and 87.5%, respectively. CONCLUSION: DECT represents an accurate imaging tool for demonstration of BME of the ankle when compared to MRI.

Magnetic resonance diffusion-tensor imaging metrics in High Grade Gliomas: Correlation with IDH1 gene status in WHO 2016 era.

PURPOSE: To evaluate any possible correlation between the presence of Isocitrate DeHydrogenase 1 mutation (IDH1m) and specific DTI (Diffusion Tensor Imaging) metrics, such as Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD). METHODS: We retrospectively analyzed 47 patients who underwent an advanced-MR study with DTI followed by surgical intervention with a subsequent histologic diagnosis of High-Grade Glioma (HGG) and immunohistochemical evaluation of IDH1 (Isocitrate DeHydrogenase) mutation status. For each DTI metrics we measured the ratio between tumor and normal tissue and we evaluated the correlation with IDH1 mutation. RESULTS: We observed a positive correlation with IDH1 status and RD and MD data. No correlation was demonstrated between IDH1 status and FA and AD. DISCUSSION: Our results support the hypothesis that the number of residual axonal fibers, extracellular matrix composition and the presence of colliquated tissue, may together contribute to a global RD increase in HGG, with a relatively higher increase in IDH1m tumors. CONCLUSIONS: Our data are in favor of a need for multimodal advance evaluation of HGG. DTI metrics help to analyze IDH1 mutation status, in order to better characterize the lesions and to tailor treatment and follow up.

Identification of residual-recurrent cholesteatoma in operated ears: diagnostic accuracy of dual-energy CT and MRI.

PURPOSE: The aim of this study was to compare the diagnostic accuracy of magnetic resonance imaging (MRI) and dual-energy computed tomography (DECT) to identify residual-recurrent cholesteatoma using the second-look surgery as the reference standard. METHODS: This prospective, institutional review board-approved study included 19 consecutive patients (11 males and 8 females; mean age of 62.2, range 34-80 years). Since five patients were studied bilaterally, a total of 24 ears were evaluated with DECT and MRI between February 2017 and June 2018. Any abnormal middle ear attenuation on high-resolution CT images (HRCT) or DECT color-coded maps, and any abnormal signal on MRI images was evaluated by four experienced radiologists. Diagnostic accuracy values of HRCT, DECT maps and CT numbers (by using receiver operator curves) and MRI were compared. Interobserver and intraobserver agreement were calculated. RESULTS: Residual-recurrent cholesteatoma was diagnosed at surgery in 16/24 ears (66.6%). MRI and DECT revealed a total of 15/16 and 14/16 cholesteatomas, respectively. The sensitivity, specificity, PPV and NPV and accuracy of MRI and DECT were 93.7, 87.5, 93.7, 87.5, and 91.6% and 87.5, 87.5, 93.3, 87.5 and 87.5%, respectively. CT numbers were significantly different between positive (mean 57.6 HU, range - 65, 112 HU) and negative cases (mean 5.4 HU, range - 100, 66 HU) with p < 0.001. The interobserver and intraobserver agreement were k = 0.87 and k = 0.83, respectively. CONCLUSION: DECT may provide an accurate demonstration of residual-recurrent middle ear cholesteatoma.

Diagnostic accuracy of dual-energy CT and virtual non-calcium techniques to evaluate bone marrow edema in vertebral compression fractures.

PURPOSE: The aim of this study was to evaluate DECT diagnostic accuracy in the identification of vertebral bone marrow edema, using MRI as standard of reference. METHODS: This prospective institutional review board-approved study included 76 consecutive patients (29 males and 47 females; mean age 62.3, range 51-82 years) studied with DECT (90 kV and tin filter 150 kV) and MRI within 7 days. Three radiologists evaluated DECT (reader 1 and 2) and MRI images (reader 3). Diagnostic accuracy of the DECT maps (qualitative assessment) and of the CT numbers (quantitative assessment), interobserver and intraobserver agreements were calculated. RESULTS: MRI revealed 61 edematous vertebrae and 52 collapsed non-edematous vertebrae. The sensitivity, specificity, PPV and NPV and accuracy of the qualitative assessment of the DECT maps were 88.6, 92.3, 93.1, 87.3 and 90.3%, for reader 1, 90.2, 90.3, 91.6, 88.7 and 90.3, for reader 2, and 91.8, 90.4, 91.6, 90.4 and 91.1% for quantitative analysis, respectively. DECT numbers were significantly different between positive (mean - 23 HU, range - 189, 29 HU) and negative cases (mean - 126 HU, range - 321, - 66 HU) with p < 0.001. The ROC curve analysis revealed an AUC of 0.886 (95% confidence interval 0.722-0.913). The interobserver and intraobserver agreements were near perfect (k = 0.87 and k = 0.83, respectively). CONCLUSION: DECT represents an accurate imaging technique for demonstrating bone marrow edema in vertebral compression fracture, if compared to MRI.

First experience and clinical results using a new non-coplanar mono-isocenter technique (HyperArc™) for Linac-based VMAT radiosurgery in brain metastases.

INTRODUCTION: Radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) is increasing in the treatment of brain metastases (BMs). Aim of the present study was to evaluate the safety and effectiveness of SRS/SFRT for BMs, using a new mono-isocenter non-coplanar solution (HyperArc™ Varian Medical System). METHODS: BMs patients with a diameter inferior to 3 cm, a life expectancy of more than 3 months and a good performance status, were eligible for Linac-based volumetric modulated arc therapy (VMAT) SFRT/SRS with HyperArc™. A retrospective analysis of patients and BMs was performed. RESULTS: From August 2017 to May 2018, 381 BMs in 64 patients were treated and 246 BMs (43 patients, median number of BMs: 5) of them were suitable for analysis. With a median FU time of 6 months, 244 out 246 (99%) BMs were controlled (18% complete response; 41% partial response, 40% stable disease), 2 BMs showed a progression, at the first control. No acute or late toxicities were reported. Median overall survival (OS) has not yet been achieved, while median time to progression was 5 months. In univariate analysis, statistically negative prognostic factors for OS were histology of primary tumor (p = 0.009): lung/breast cancer had better survival rates as compared to others. Cumulative intracranial volume disease ≥ 15 cc and systemic progression disease were independent prognostic factors for OS at univariate (p = 0.04; p = 0.005) and multivariate (p = 0.04; p = 0.009) analysis, respectively. CONCLUSION: The present first clinical data show that SFRT/SRS with HyperArc™ is safe and effective for BMs patients. The utilization of SFRT/SRS for BMs is promising and should be further explored in randomized trials.

Surprising complete response of intramedullary spinal cord metastasis from breast cancer: a case report and literature review.

PURPOSE: Intramedullary spinal cord metastases (ISCM) are considered rare but their incidence is rising. Most ISCM cases are recognized to occur in patients with stage IV lung cancer or breast cancer (BC). METHODS: We report a rare case of cervical BC-ISCM in 60-year-old woman, documented by magnetic resonance imaging and positron emission tomography-computed tomography and treated with volumetric modulated arc therapy with daily image-guided radiation therapy (VMAT/IGRT). RESULTS: An unexpected clinical and radiologic complete response in absence of neurologic side effects was recorded 4 months after VMAT/IGRT. CONCLUSIONS: The present case report shows the feasibility of advanced RT and its optimal response in a case of ISCM from BC. Despite the short follow-up, in comparison with available literature data concerning the management of BC-ISCM, we found an early complete response, in contrast with other reported experiences.

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. © 2016 Wiley Periodicals, Inc.

Test-retest reliability of the default mode network in a multi-centric fMRI study of healthy elderly: Effects of data-driven physiological noise correction techniques.

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc.

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.

Leksell Gamma Knife for pediatric and adolescent cerebral arteriovenous malformations: results of 100 cases followed up for at least 36 months.

OBJECT: The goal of this study was to evaluate advantages, risks, and failures of Gamma Knife radiosurgery (GKRS) in a large series of pediatric and adolescent patients with cerebral arteriovenous malformations (cAVMs) who were followed up for at least 36 months. METHODS: Since February 1993, 100 pediatric and adolescent patients (≤ 18 years of age) with cAVMs have undergone GKRS at the authors' institution and were followed up for at least 36 months. Forty-six patients were boys and 54 were girls; the mean age was 12.8 years (range 3-18 years). Hemorrhage, either alone or combined with seizure, was the clinical onset in 70% of cases. The mean pre-GK cAVM volume was 2.8 ml; 92% of cAVMs were Spetzler-Martin (S-M) Grades I-III. Most lesions (94%) were in eloquent or deep-seated brain regions, according to S-M classification. The parameters for mean and range in treatment planning were prescription isodose 53.8% (40%-90%); prescription dose (PD) 20.2 Gy (9.0-26.4 Gy); maximal dose (MD) 37.8 Gy (18-50 Gy); and number of shots 4.7 (1-17). On the day of GKRS, stereotactic CT or stereotactic MRI and digital subtraction angiography were used. RESULTS: Obliteration rate (OR) was angiographically documented in 75 of 84 cases (89.3%) after single-session GKRS, with actuarial ORs at 3 and 5 years of 68.0% and 88.1%, respectively. A repeat treatment was performed in 7 patients (6 with obliteration), and 16 patients with cAVMs underwent staged treatment (9 of them were angiographically cured). Thus, the overall OR was 90%, with actuarial ORs at 3, 5, and 8 years of 59.0%, 76.0%, and 85.0%, respectively. Permanent symptomatic GK-related complications were observed in 11% of cases, with surgical removal of enlarged mass seen on post-RS imaging needed in 5 cases. Hemorrhage during the latency period occurred in 9% of patients, but surgical evacuation of the hematoma was required in only 1 patient. One patient died due to rebleeding of a brainstem cAVM. Radiosurgery outcomes varied according to cAVM sizes and doses: volumes ≤ 10 ml and PDs > 16 Gy were significantly associated with higher ORs and lower rates of permanent complication and bleeding during the latency period. CONCLUSIONS: The data from this study reinforce the conclusion that GKRS is a safe and effective treatment for pediatric and adolescent cAVMs, yielding a high OR with minimal permanent severe morbidity and no mortality. The very low frequency of severe hemorrhages during the latency period further encourages a widespread application of RS in such patients. Univariate analysis found that modified RS-based cAVM score, nidus volume, PD, integral dose, S-M grade, and preplanned treatment (the last 2 parameters were also confirmed on multivariate analysis) significantly influenced OR. Lower S-M grades and single-session planned treatments correlated with shorter treatment obliteration interval on univariate analysis. This statistical analysis suggests that a staged radiosurgical treatment should be planned when nidus volume > 10 ml and/or when the recommended PD is ≤ 16 Gy.

Behavioral and neural correlates of visual emotion discrimination and empathy in mild cognitive impairment.

Emotional and social cognitive deficits were investigated in a group of 24 individuals with mild cognitive impairment (MCI) and 24 healthy controls. Empathic and visual emotional responses were collected, analyzed and correlated to brain structural imaging data by means of: (i) a pictorial matching-to-sample task with facial and non-facial stimuli; (ii) self-reported questionnaires for cognitive and affective emotional components, and alexithymia; (iii) in-depth assessment of cognitive functions. Results indicated that visual processing of faces in MCI individuals did not benefit from fearful emotional content which in healthy controls facilitates stimulus' recognition (emotional enhancement effect). This implicit visuo-emotional disorder was specific for the faces, did not generalize to other categories, and did not correlate to explicit measures of empathy. Thus, our main finding indicates that in MCI individuals, deficits in visual recognition of facial emotions may arise already in the earliest stages of memorization, during the visual encoding of facial emotions. Voxel-based morphometry revealed its association with atrophy in frontal and occipito-temporal regions, mostly involving the anterior medial prefrontal cortex (P<0.05, multiple-comparison correction). Neural evidences were corroborated by clinical scores showing significant correlation between reduction of Emotion Enhancement Effect and deficits in frontal/executive functions. Crucially, the disorder did not appear to be related to the number of impaired cognitive domains (single or multiple-domain MCI) but rather to the involvement of frontal brain networks and frontal/executive functions. This suggests that in prodromal stages of dementia, frontal symptoms may represent a significant signal of emotional recognition disorders.

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 DICE > 0.90), good for CA1 and presubiculum (reproducibility error ∼ 5% and DICE ∼ 0.90), and poorer for fimbria and hippocampal fissure (reproducibility error ∼ 15% and DICE < 0.80). Spearman's 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.

Patient-specific detection of cerebral blood flow alterations as assessed by arterial spin labeling in drug-resistant epileptic patients.

Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients.

Diffuse alterations in grey and white matter associated with cognitive impairment in Shwachman-Diamond syndrome: evidence from a multimodal approach.

Shwachman-Diamond syndrome is a rare recessive genetic disease caused by mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal dysplasia and variable cognitive impairments. Structural brain abnormalities (smaller head circumference and decreased brain volume) have also been reported. No correlation studies between brain abnormalities and neuropsychological features have yet been performed. In this study we investigate neuroanatomical findings, neurofunctional pathways and cognitive functioning of Shwachman-Diamond syndrome subjects compared with healthy controls. To be eligible for inclusion, participants were required to have known SBDS mutations on both alleles, no history of cranial trauma or any standard contraindication to magnetic resonance imaging. Appropriate tests were used to assess cognitive functions. The static images were acquired on a 3 × 0 T magnetic resonance scanner and blood oxygen level-dependent functional magnetic resonance imaging data were collected both during the execution of the Stroop task and at rest. Diffusion tensor imaging was used to assess brain white matter. The Tract-based Spatial Statistics package and probabilistic tractography were used to characterize white matter pathways. Nine participants (5 males), half of all the subjects aged 9-19 years included in the Italian Shwachman-Diamond Syndrome Registry, were evaluated and compared with nine healthy subjects, matched for sex and age. The patients performed less well than norms and controls on cognitive tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both in the left (+10%) and in the right (+15%) hemisphere, significantly differently increased in the temporal (left and right, p = 0.04), and right parietal (p = 0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The greatest increases were observed in the left limbic-anterior cingulate cortex (≥43%, p < 0.0004). Only in Broca's area in the left hemisphere did the patients show a thinner cortical thickness than that of controls (p = 0.01). Diffusion tensor imaging showed large, significant difference increases in both fractional anisotropy (+37%, p < 0.0001) and mean diffusivity (+35%, p < 0.005); the Tract-based Spatial Statistics analysis identified six abnormal clusters of white matter fibres in the fronto-callosal, right fronto-external capsulae, left fronto-parietal, right pontine, temporo-mesial and left anterior-medial-temporal regions. Brain areas activated during the Stroop task and those active during the resting state, are different, fewer and smaller in patients and correlate with worse performance (p = 0.002). Cognitive impairment in Shwachman-Diamond syndrome subjects is associated with diffuse brain anomalies in the grey matter (verbal skills with BA44 and BA20 in the right hemisphere; perceptual skills with BA5, 37, 20, 21, 42 in the left hemisphere) and white matter connectivity (verbal skills with alterations in the fronto-occipital fasciculus and with the inferior-longitudinal fasciculus; perceptual skills with the arcuate fasciculus, limbic and ponto-cerebellar fasciculus; memory skills with the arcuate fasciculus; executive functions with the anterior cingulated and arcuate fasciculus).