Association between renal insufficiency and lesion characteristics of posterior reversible encephalopathy syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized by cerebral blood flow dysregulation and the blood-brain barrier (BBB) disruption. While renal insufficiency has been considered a factor in BBB fragility, the relationship between renal insufficiency and the PRES lesions volume remains unclear. METHODS: This observational study was performed retrospectively. PRES patients were categorized into two groups with renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 on the day of symptom occurrence. Lesion volume was measured using fluid-attenuated inversion recovery (FLAIR) imaging, and the brain was divided into nine regions. The volume of the parietal-occipital-temporal lobe was considered typical, while the other six regions were labeled as atypical. RESULTS: The study included 200 patients, of whom 94 (47%) had renal insufficiency. Patients with renal insufficiency had a larger lesion volume (144.7 ± 125.2 cc) compared to those without renal insufficiency (110.5 ± 93.2 cc; p = 0.032); particularly in the atypical lesions volume (49.2 ± 65.0 vs. 29.2 ± 44.3 cc; p = 0.013). However, there was no difference in the reversibility of the lesions (35.2 ± 67.5 vs. 18.8 ± 33.4 cc; p = 0.129). Multiple regression analysis revealed that decreases in eGFR (ß = -0.34, 95% CI -0.62-0.05, p = 0.020) were positively associated with total lesion volume. CONCLUSION: Our findings suggest that PRES patients with renal insufficiency experience more severe lesion volumes, likely due to the atypical brain regions involvement. The lesions involving atypical regions may have a similar pathophysiology to typical lesions, as the PRES lesions reversibility was found to be similar between individuals with and without renal insufficiency.

The association of endodontic prognostic factors with the presence of periapical lesion, its volume, and bone characteristics in endodontically treated molars: a cross-sectional study.

BACKGROUND: This study intended to evaluate the association between several endodontic prognostic factors with the presence of periapical lesions (PLs), their volume, and bone characteristics including cortical bone destruction (CBD) and buccal plate bone height (BPBH) in root-filled molar teeth using cone-beam computed tomography. METHODS: A collection of 143 scans of endodontically treated maxillary/mandibular first or second molars recorded over 8 years, were obtained from a specialized radiology center. Data on prognostic factors including tooth number, gender, jaw type, the status and number of missed canals, obturation length, restoration type, presence of a separated instrument, presence of a post or screw in the canals, and presence of perforation were collected. The assessed outcomes included PL presence, PL volume, CBD, and BPBH. The association between prognostic factors and outcomes was evaluated using multiple logistic regression models with adjusted covariates and multifactorial ANOVA at a significance level of 0.05. RESULTS: A total of 282 molars from 82 women and 50 men with a mean age of 40.6 ± 12.27 were included. Among those, 139 teeth presented PL with a mean volume of 18.68 mm3. CBD was prevalent in 137 teeth and the mean BPBH appeared to be 9.45 mm. The presence of a missed canal (OR = 10.022, P < .05), underfilled canal (OR = 3.725, P < .05), overfilled canal (OR = 15.859, P = .018), and perforation (OR = 15.261, P = .013) was significantly associated with PLs. None of the prognostic factors could considerably contribute to the CBD (P > .05). The presence of a missed canal was positively associated with the PL volume (P < .05). Similarly, missed canals (P < .05), perforation (P < .05), and separated instruments (P = .004) were associated with a significantly reduced BPBH. CONCLUSIONS: Overfillings, perforations, missed canals, and underfillings were identified as remarkable predictors of PL, arranged in descending order of their respective impact. The only factor capable of significantly increasing the PL volume was the missed canal. In brief, obturation length errors, perforations, missed canals, and separated instruments were robustly correlated with endodontic failure, which highlights the importance of mitigating the potential for errors by following the fundamentals of endodontics.

Ambient circulation surrounding an ablation catheter tip affects ablation lesion characteristics.

INTRODUCTION: The association between ambient circulating environments (CEs) and ablation lesions has been largely underexplored. METHODS: Viable bovine myocardium was placed in a saline bath in an ex vivo endocardial model. Radiofrequency (RF) ablation was performed using three different ablation catheters: 3.5 mm open irrigated (OI), 4, and 8 mm. Variable flow rates of surrounding bath fluids were applied to simulate standard flow, high flow, and no flow. For in vivo epicardial ablation, 24 rats underwent a single OI ablation and performed with circulating saline (30 ml/min; n = 12), versus those immersed in saline without circulation (n = 12). RESULTS: High flow reduced ablation lesion volumes for all three catheters. In no-flow endocardial CE, both 4 mm and OI catheters produced smaller lesions compared with standard flow. However, the 8 mm catheter produced the largest lesions in a no-flow CE. Ablation performed in an in vivo model with CE resulted in smaller lesions compared with ablation performed in a no-flow environment. No statistically significant differences in steam pops were found among the groups. CONCLUSION: A higher endocardial CE flow can decrease RF effectiveness. Cardiac tissue subjected to no endocardial CE flow may also limit RF for 4 mm catheters, but not for OI catheters; these findings may have implications for RF ablation safety and efficacy, especially in the epicardial space without circulating fluid or in the endocardium under varying flow conditions.

Pregnancy-induced brain magnetic resonance imaging changes in women with multiple sclerosis.

BACKGROUND AND PURPOSE: The effect of pregnancy on brain changes and radiological disease activity in women with multiple sclerosis (MS) is not well understood. This study was undertaken to describe the dynamics of lesion activity and brain volume changes during the pregnancy and postpartum periods. METHODS: This observational study of 62 women with relapsing-remitting MS included magnetic resonance imaging (221 scans) as well as clinical visits at baseline (<24 and >6 months before pregnancy), prepregnancy (<6 months before pregnancy), postpartum (<3 months after delivery), and follow-up (>12 and <24 months after delivery) periods. RESULTS: The majority of women had a mild disability and a short disease duration (median = 5.5 years). Eighteen (29.0%) women had a relapse during the year preceding pregnancy onset, nine (14.5%) during pregnancy, and 20 (32.3%) in the year following delivery. Disability status remained unchanged during follow-up. Women in the postpartum period (n = 62) had higher T2 lesion volume (median = 1.18 ml vs. 0.94 ml), greater annualized T2 lesion volume increase (0.23 ml vs. 0.0 ml), lower brain parenchymal fraction (85.6% vs. 86.4%), and greater annualized brain volume loss (-1.74% vs. -0.16%) compared with the prepregnancy period (all p < 0.001). At 12-24 months after delivery, women (n = 41) had higher T2 lesion volume (1.16 ml vs. 1.0 ml) and lower brain parenchymal fraction (86.0% vs. 86.5%) compared to the prepregnancy period (both p < 0.001). CONCLUSIONS: The postpartum period was associated with an increase in T2 lesion volume and accelerated brain volume loss in a considerable proportion of women. This should be considered in treatment decision-making and designing clinical trials.

Variability assessment of manual segmentations of ischemic lesion volume on 24-h non-contrast CT.

PURPOSE: Infarct lesion volume (ILV) may serve as an imaging biomarker for clinical outcomes in the early post-treatment stage in patients with acute ischemic stroke. The aim of this study was to evaluate the inter- and intra-rater reliability of manual segmentation of ILV on follow-up non-contrast CT (NCCT) scans. METHODS: Fifty patients from the Prove-IT study were randomly selected for this analysis. Three raters manually segmented ILV on 24-h NCCT scans, slice by slice, three times. The reference standard for ILV was generated by the Simultaneous Truth And Performance Level estimation (STAPLE) algorithm. Intra- and inter-rater reliability was evaluated, using metrics of intraclass correlation coefficient (ICC) regarding lesion volume and the Dice similarity coefficient (DSC). RESULTS: Median age of the 50 subjects included was 74.5 years (interquartile range [IQR] 67-80), 54% were women, median baseline National Institutes of Health Stroke Scale was 18 (IQR 11-22), median baseline ASPECTS was 9 (IQR 6-10). The mean reference standard ILV was 92.5 ml (standard deviation (SD) ± 100.9 ml). The manually segmented ILV ranged from 88.2 ± 91.5 to 135.5 ± 119.9 ml (means referring to the variation between readers, SD within readers). Inter-rater ICC was 0.83 (95%CI: 0.76-0.88); intra-rater ICC ranged from 0.85 (95%CI: 0.72-0.92) to 0.95 (95%CI: 0.91-0.97). The mean DSC among the three readers ranged from 65.5 ± 22.9 to 76.4 ± 17.1% and the mean overall DSC was 72.8 ± 23.0%. CONCLUSION: Manual ILV measurements on follow-up CT scans are reliable to measure the radiological outcome despite some variability.

The ketone ester, 3-hydroxybutyl-3-hydroxybutyrate, attenuates neurobehavioral deficits and improves neuropathology following controlled cortical impact in male rats.

Traumatic brain injury (TBI) is a leading cause of human death and disability with no effective therapy to fully prevent long-term neurological deficits in surviving patients. Ketone ester supplementation is protective in animal models of neurodegeneration, but its efficacy against TBI pathophysiology is unknown. Here, we assessed the neuroprotective effect of the ketone monoester, 3-hydroxybutyl-3-hydroxybutyrate, (KE) in male Sprague Dawley rats (n=32). TBI was induced using the controlled cortical impact (CCI) with Sham animals not receiving the brain impact. KE was administered daily by oral gavage (0.5 ml/kg/day) and provided ad libitum at 0.3% (v/v) in the drinking water. KE supplementation started immediately after TBI and lasted for the duration of the study. Motor and sensory deficits were assessed using the Neurobehavioral Severity Scale-Revised (NSS-R) at four weeks post-injury. The NSS-R total score in CCI + KE (1.2 ± 0.4) was significantly lower than in CCI + water (4.4 ± 0.5). Similarly, the NSS-R motor scores in CCI + KE (0.6 ± 0.7) were significantly lower than CCI + water (2.9 ± 1.5). Although the NSS-R sensory score in the CCI + KE group (0.5 ± 0.2) was significantly lower compared to CCI + water (1.8 ± 0.4), no difference was observed between CCI + water and Sham + water (1.0 ± 0.2) groups. The lesion volume was smaller in the CCI + KE (10 ± 3 mm3) compared to CCI + water (47 ± 11 mm3; p < 0.001). KE significantly decreased Iba1+ stained areas in the cortex and hippocampus, and GFAP+ stained areas in all brain regions analyzed - prefrontal cortex, hippocampus, cortex, amygdala (p < 0.01). In summary, our results indicate that KE can protect against TBI-induced morphological and functional deficits when administered immediately after an insult.

A method for labelling lesions for machine learning and some new observations on osteochondrosis in computed tomographic scans of four pig joints.

BACKGROUND: Osteochondrosis is a major cause of leg weakness in pigs. Selection against osteochondrosis is currently based on manual scoring of computed tomographic (CT) scans for the presence of osteochondrosis manifesta lesions. It would be advantageous if osteochondrosis could be diagnosed automatically, through artificial intelligence methods using machine learning. The aim of this study was to describe a method for labelling articular osteochondrosis lesions in CT scans of four pig joints to guide development of future machine learning algorithms, and to report new observations made during the labelling process. The shoulder, elbow, stifle and hock joints were evaluated in CT scans of 201 pigs. RESULTS: Six thousand two hundred fifty osteochondrosis manifesta and cyst-like lesions were labelled in 201 pigs representing a total volume of 211,721.83 mm3. The per-joint prevalence of osteochondrosis ranged from 64.7% in the hock to 100% in the stifle joint. The lowest number of lesions was found in the hock joint at 208 lesions, and the highest number of lesions was found in the stifle joint at 4306 lesions. The mean volume per lesion ranged from 26.21 mm3 in the shoulder to 42.06 mm3 in the elbow joint. Pigs with the highest number of lesions had small lesions, whereas pigs with few lesions frequently had large lesions, that have the potential to become clinically significant. In the stifle joint, lesion number had a moderate negative correlation with mean lesion volume at r = - 0.54, p < 0.001. CONCLUSIONS: The described labelling method is an important step towards developing a machine learning algorithm that will enable automated diagnosis of osteochondrosis manifesta and cyst-like lesions. Both lesion number and volume should be considered during breeding selection. The apparent inverse relationship between lesion number and volume warrants further investigation.

Relation between the size of patent foramen ovale and the volume of acute cerebral ischemic lesion in young patients with cryptogenic ischemic stroke.

BACKGROUND: Patent foramen ovale (PFO) closure is superior to medical therapy alone to prevent stroke recurrence in selected patients. Small cortical infarcts and large right to left shunts seem to identify patients who will benefit most from closure. We aimed to study the correlation between the size of the PFO and the volume of cerebral ischemic lesions in young patients with cryptogenic ischemic stroke. METHODS: PFO dimensions and acute ischemic lesion volume of 20 patients, aged<55 years, were analyzed with transesophageal echocardiography and brain magnetic resonance imaging, respectively. The association between the volume of ischemic lesions with the length of PFO, maximum separation between septum primum and septum secundum, and the combination of the twos was explored. RESULTS: A direct statistically significant correlation was found between cerebral lesion volume and maximum separation of septum primum and septum secundum (p=0.047). Length of PFO showed a non-significant trend towards an inverse correlation with lesion volume (p=0.603). Multiple linear regression analysis showed that cerebral lesion volume was dependent directly on maximum separation and inversely on length of PFO (regression coeff. -0,837; p= 0.057; 2,536, p=0.006, respectively). CONCLUSIONS: These data suggest that even small PFO might be pathogenetic in case of small cerebral infarcts and that large cerebral infarcts might be PFO related if the shunt is large. If confirmed, the combination of detailed characteristics of PFO with the volume of cerebral infarct could be integrated in a new score to select patients who would take real advantage from a percutaneous closure.

Relationships among language ability, the arcuate fasciculus and lesion volume in patients with putaminal hemorrhage: a diffusion tensor imaging study.

Relationships among language ability, arcuate fasciculus and lesion volume were investigated by use of diffusion tensor tractography in patients with putaminal hemorrhage. Thirty-three right-handed patients within six weeks of hemorrhage onset were recruited. Correlation of the aphasia quotient with subset (fluency, comprehension, repetition, naming) scores, diffusion tensor tractography parameters and lesion volume of patients, aphasia quotient (r = 0.446) with subset (naming: r = 0.489) score had moderate positive correlations with fractional anisotropy of the left arcuate fasciculus. The aphasia quotient subset (repetition) score had a strong positive correlation with fractional anisotropy of the left arcuate fasciculus (r = 0.520), whereas, aphasia quotient subset (fluency and comprehension) scores had no significant correlations with fractional anisotropy of the left arcuate fasciculus after Benjamini-Hochberg correction. Aphasia quotient (r = 0.668) with subset (fluency: r = 0.736, comprehension: r = 0.739, repetition: r = 0.649, naming: r = 0.766) scores had strong positive correlations with the tract volume of the left arcuate fasciculus and strong negative correlations with lesion volume (r = -0.521, fluency: r = -0.520, comprehension: r = -0.513, repetition: r = -0.518, naming: r = -0.562). Fractional anisotropy of the left arcuate fasciculus had a moderate negative correlation with lesion volume (r = -0.462), whereas the tract volume of the left arcuate fasciculus had a strong negative correlation with lesion volume (r = -0.700). According to the result of mediation analysis, tract volume of the left arcuate fasciculus fully mediated the effect of lesion volume on the aphasia quotient. Regarding the receiver operating characteristic curve, the lesion volume cut-off value was 29.17 cm3 and the area under the curve (0.74), sensitivity (0.77) and specificity (0.80) were higher than those of fractional anisotropy, tract volume and aphasia quotient cut-off values. It was found that level of language disability was related to lesion volume as well as to injury severity of arcuate fasciculus in the dominant hemisphere of patients with putaminal hemorrhage. In particular, the tract volume of the arcuate fasciculus in the dominant hemisphere fully mediated the effect of lesion volume on language ability. Additionally, a lesion volume of approximately 30 cm3 was helpful in discriminating arcuate fasciculus discontinuation in the dominant hemisphere.

Does vascular stiffness predict white matter hyperintensity burden in ischemic heart disease with preserved ejection fraction?

The survival rate of patients with ischemic heart disease (IHD) is increasing. However, survivors experience increased risk for neurological complications. The mechanisms for this increased risk are unknown. We tested the hypothesis that patients with IHD have greater carotid and cerebrovascular stiffness, and these indexes predict white matter small vessel disease. Fifty participants (age, 40-78 yr), 30 with IHD with preserved ejection fraction and 20 healthy age-matched controls, were studied using ultrasound imaging of the common carotid artery (CCA) and middle cerebral artery (MCA), as well as magnetic resonance imaging (T1, T2-FLAIR), to measure white matter lesion volume (WMLv). Carotid ß-stiffness provided the primary measure of peripheral vascular stiffness. Carotid-cerebral pulse wave transit time (ccPWTT) provided a marker of cerebrovascular stiffness. Pulsatility index (PI) and resistive index (RI) of the MCA were calculated as measures of downstream cerebrovascular resistance. When compared with controls, patients with IHD exhibited greater ß-stiffness [8.5 ± 3.3 vs. 6.8 ± 2.2 arbitrary units (AU); P = 0.04], MCA PI (1.1 ± 0.20 vs. 0.98 ± 0.18 AU; P = 0.02), and MCA RI (0.66 ± 0.06 vs. 0.62 ± 0.07 AU; P = 0.04). There was no difference in WMLv between IHD and control groups (0.95 ± 1.2 vs. 0.86 ± 1.4 mL; P = 0.81). In pooled patient data, WMLv correlated with both ß-stiffness (R = 0.34, P = 0.02) and cerebrovascular ccPWTT (R = -0.43, P = 0.02); however, ß-stiffness and ccPWTT were not associated (P = 0.13). In multivariate analysis, WMLv remained independently associated with ccPWTT (P = 0.02) and carotid ß-stiffness (P = 0.04). Patients with IHD expressed greater ß-stiffness and cerebral microvascular resistance. However, IHD did not increase risk of WMLv or cerebrovascular stiffness. Nonetheless, pooled data indicate that both carotid and cerebrovascular stiffness are independently associated with WMLv.NEW & NOTEWORTHY This study found that patients with ischemic heart disease (IHD) with preserved ejection fraction and normal blood pressures exhibit greater carotid ß-stiffness, as well as middle cerebral artery pulsatility and resistive indexes, than controls. White matter lesion volume (WMLv) was not different between vascular pathology groups. Cerebrovascular pulse wave transit time (ccPWTT) and carotid ß-stiffness independently associate with WMLv in pooled participant data, suggesting that regardless of heart disease history, ccPWTT and ß-stiffness are associated with structural white matter damage.

Should frequent MRI monitoring be performed in natalizumab-treated MS patients? A contribution to a recent debate.

BACKGROUND: Brain magnetic resonance imaging (MRI) is the most effective surveillance tool for the detection of asymptomatic progressive multifocal leukoencephalopathy (PML). However, the optimal frequency for routine MRI surveillance is under-investigated. OBJECTIVE: To understand whether, upon their first MRI appearance, PML lesions present a difference in volume when comparing patients who frequently underwent MRI surveillance (3/4 months) with those who were assessed at longer intervals (6/12 months) and to understand the impact of the volume of lesions on clinical outcome. METHODS: The data of patients included in the Italian PML cohort were retrospectively analysed. Patients who had all the pre-diagnostic MRI scans available (n = 37) were included. The volume of PML lesion was calculated by manually outlining the PML lesion. RESULTS: Compared with patients who underwent MRI examination at least every 4 months, patients who were assessed less frequently had a lesion of significantly higher volume (median: 2567 (883-3583) vs. 664 mm3 (392-963) p = 0.006) and suffered a higher rate of disability (median: 2.25 expanded disability status scale points (-2.5 to 8) vs. 0.5 (-1 to 2.5) p = 0.004). CONCLUSION: The positive clinical outcome of patients undergoing frequent MRI surveillance and the small volume of the PML lesion upon first appearance justify a frequent surveillance using MRI in patients at high risk of PML.

A novel classification of fatigue in multiple sclerosis based on longitudinal assessments.

BACKGROUND: Magnetic resonance imaging (MRI) studies of multiple sclerosis-related fatigue had limited reproducibility. Temporal fatigue fluctuations have not been considered. OBJECTIVE: To investigate whether a novel group allocation that reflects temporal dynamics of fatigue improves our ability to detect fatigue-associated structural brain abnormalities. METHODS: Patient stratification based on biennial fatigue assessments: sustained fatigue (SF, n = 29, fatigued at the latest ⩾2 assessments), one time-point fatigue (1F, n = 15, fatigued at the latest, but non-fatigued at the penultimate assessment), reversible fatigue (RF, n = 31, non-fatigued at the latest assessment, but reported fatigue previously), and never fatigued (NF, n = 54). Brain parenchymal fraction (BPF) and T2 lesion volume (T2LV) were compared between these groups and were derived using a conventional, single time-point fatigued versus non-fatigued stratification. RESULTS: The SF versus NF stratification yielded improved power. SF (p = 0.005) and RF (p = 0.043) showed significantly higher T2LV than NF. T2LV showed no significant differences in SF versus 1F, SF versus RF, or 1F versus RF. Fatigued versus non-fatigued patients showed significantly higher T2LV (p = 0.030). We found no significant differences in BPF between the groups. CONCLUSION: Taking into account temporal fatigue dynamics increases the statistical power with respect to T2LV and may improve characterization of brain pathological correlates of MS-related fatigue.

Single MRI-Based Volumetric Assessment in Clinical Practice Is Associated With MS-Related Disability.

BACKGROUND: The added value of brain volume measurements in the clinical practice of multiple sclerosis (MS) has been questioned. PURPOSE: To investigate the contribution of volume measures obtained with magnetic resonance scans performed as part of regular care to predict measures of cognitive and physical MS disability in a real-world setting. STUDY TYPE: Retrospective. SUBJECTS: In all, 470 adults with diagnosed MS. FIELD STRENGTH/SEQUENCE: 3D fluid attenuation inversion recovery (FLAIR) and 3D T1 -weighted MR images at 3.0T MR. ASSESSMENT: Lesion and brain volume were measured by an automated method, MSmetrix, developed by icometrix. STATISTICAL TESTS: We used stepwise linear regression models to assess the added value of a single volumetric assessment in predicting Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). Brain volumes categorized into quartiles were used as predictive variables in a time-to-event analysis and Cox proportional hazard regression with time to worsening from baseline as outcome measures. RESULTS: Brain and lesion volume in relapsing onset MS strongly contributed to the best models, with a substantial role for age in the EDSS model and a modest role for education in the SDMT model. Adding MR volumetric information increased the explained variance from 17% to 28% in the best model for EDSS and from 9% to 25% in the best model for SDMT. A significantly reduced hazard (P < 0.05) of SDMT worsening was found in the highest normalized brain volume quartiles (1375-1608 ml), compared with the lowest quartile (1201-1374 ml) in the total study population. DATA CONCLUSION: Our findings indicate that a single brain volumetric assessment contributes to the prediction of MS-related disability, with distinct patterns for EDSS as a measure of physical disability, and SDMT as a measure of cognitive disability. A threshold effect for the lowest brain volumes with regard to SDMT worsening over time was found. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1312-1321.

Brain regional volume estimations with NeuroQuant and FIRST: a study in patients with a clinically isolated syndrome.

PURPOSE: Brain volume estimates from magnetic resonance images (MRIs) are of great interest in multiple sclerosis, and several automated tools have been developed for this purpose. The goal of this study was to assess the agreement between two tools, NeuroQuant® (NQ) and FMRIB's Integrated Registration Segmentation Tool (FIRST), for estimating overall and regional brain volume in a cohort of patients with a clinically isolated syndrome (CIS). In addition, white matter lesion volume was estimated with NQ and the Lesion Segmentation Toolbox (LST). METHODS: One hundred fifteen CIS patients were analysed. Structural images were acquired on a 3.0-T system. The volume agreement between methods (by estimation of the intraclass correlation coefficient) was calculated for the right and left thalamus, caudate, putamen, pallidum, hippocampus, and amygdala, as well as for the total intracranial volume and white matter lesion volume. RESULTS: In general, the estimated volumes were larger by NQ than FIRST, except for the pallidum. Agreement was low (ICC < 0.40) for the smaller structures (amygdala and pallidum) and fair to good (ICC > 0.40) for the remaining ones. Agreement was fair for lesion volume (ICC = 0.61), with NQ estimates lower than LST. CONCLUSIONS: Agreement between NQ and FIRST brain volume estimates depends on the size of the structure of interest, with larger volumes achieving better agreement. In addition, concordance between the two tools does seem to be dependent on the presence of brain lesions.

A multivariate lesion symptom mapping toolbox and examination of lesion-volume biases and correction methods in lesion-symptom mapping.

Lesion-symptom mapping has become a cornerstone of neuroscience research seeking to localize cognitive function in the brain by examining the sequelae of brain lesions. Recently, multivariate lesion-symptom mapping methods have emerged, such as support vector regression, which simultaneously consider many voxels at once when determining whether damaged regions contribute to behavioral deficits (Zhang, Kimberg, Coslett, Schwartz, & Wang, ). Such multivariate approaches are capable of identifying complex dependences that traditional mass-univariate approach cannot. Here, we provide a new toolbox for support vector regression lesion-symptom mapping (SVR-LSM) that provides a graphical interface and enhances the flexibility and rigor of analyses that can be conducted using this method. Specifically, the toolbox provides cluster-level family-wise error correction via permutation testing, the capacity to incorporate arbitrary nuisance models for behavioral data and lesion data and makes available a range of lesion volume correction methods including a new approach that regresses lesion volume out of each voxel in the lesion maps. We demonstrate these new tools in a cohort of chronic left-hemisphere stroke survivors and examine the difference between results achieved with various lesion volume control methods. A strong bias was found toward brain wide lesion-deficit associations in both SVR-LSM and traditional mass-univariate voxel-based lesion symptom mapping when lesion volume was not adequately controlled. This bias was corrected using three different regression approaches; among these, regressing lesion volume out of both the behavioral score and the lesion maps provided the greatest sensitivity in analyses.

Conventional and advanced MRI in multiple sclerosis.

Magnetic resonance imaging (MRI) plays a central role in the management of patients with multiple sclerosis (MS). T2-weighted/FLAIR lesions have been included in the diagnostic criteria since 2001, and the importance of the technology has been expanded in each successive revision of the McDonald criteria. While the typical focal hyperintense lesions seen on T2 and FLAIR sequences in several areas of the central nervous system are key features for MS diagnosis, they can also be used to monitor disease activity, particularly in asymptomatic patients, and to evaluate therapeutic responses. The development of new lesions, particularly in medullary and infratentorial locations, is a strong predictor of long-term disability and risk of evolution to a secondary-progressive phase. Yet, changes in T2 lesion volume are poor predictors of subsequent disease evolution in many cases, a situation often referred to as the "clinicoradiological paradox". Nevertheless, advanced MRI techniques allow quantification of several pathological processes in vivo and offer insights into MS pathophysiology beyond white matter lesions. By investigating what is happening beneath the visible surface of MS pathology, these techniques not only help to unravel the clinicoradiological paradox, but also provide early measures of functional and structural tissue abnormalities before the advent of irreversible neurodegeneration.

The loss-of-function disease-mutation G301R in the Na+/K+-ATPase α2 isoform decreases lesion volume and improves functional outcome after acute spinal cord injury in mice.

BACKGROUND: The Na+/K+-ATPases are transmembrane ion pumps important for maintenance of ion gradients across the plasma membrane that serve to support multiple cellular functions, such as membrane potentials, regulation of cellular volume and pH, and co-transport of signaling transmitters in all animal cells. The α2Na+/K+-ATPase subunit isoform is predominantly expressed in astrocytes, which us the sharp Na+-gradient maintained by the sodium pump necessary for astroglial metabolism. Prolonged ischemia induces an elevation of [Na+]i, decreased ATP levels and intracellular pH owing to anaerobic metabolism and lactate accumulation. During ischemia, Na+/K+-ATPase-related functions will naturally increase the energy demand of the Na+/K+-ATPase ion pump. However, the role of the α2Na+/K+-ATPase in contusion injury to the spinal cord remains unknown. We used mice heterozygous mice for the loss-of-function disease-mutation G301R in the Atp1a2 gene (α 2+/G301R ) to study the effect of reduced α2Na+/K+-ATPase expression in a moderate contusion spinal cord injury (SCI) model. RESULTS: We found that α 2+/G301R mice display significantly improved functional recovery and decreased lesion volume compared to littermate controls (α 2+/+ ) 7 days after SCI. The protein level of the α1 isoform was significantly increased, in contrast to the α3 isoform that significantly decreased 3 days after SCI in both α 2+/G301R and α 2+/+ mice. The level of the α2 isoform was significantly decreased in α 2+/G301R mice both under naïve conditions and 3 days after SCI compared to α 2+/+ mice. We found no differences in astroglial aquaporin 4 levels and no changes in the expression of chemokines (CCL2, CCL5 and CXCL1) and cytokines (TNF, IL-6, IL-1ß, IL-10 and IL-5) between genotypes, just as no apparent differences were observed in location and activation of CD45 and F4/80 positive microglia and infiltrating leukocytes. CONCLUSION: Our proof of concept study demonstrates that reduced expression of the α2 isoform in the spinal cord is protective following SCI. Importantly, the BMS and lesion volume were assessed at 7 days after SCI, and longer time points after SCI were not evaluated. However, the α2 isoform is a potential possible target of therapeutic strategies for the treatment of SCI.

Lesion volume predicts prostate cancer risk and aggressiveness: validation of its value alone and matched with prostate imaging reporting and data system score.

OBJECTIVE: To demonstrate the association between magnetic resonance imaging (MRI) estimated lesion volume (LV), prostate cancer detection and tumour clinical significance, evaluating this variable alone and matched with Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. PATIENTS AND METHODS: We retrospectively analysed 157 consecutive patients, with at least one prior negative systematic prostatic biopsy, who underwent transperineal prostate MRI/ultrasonography fusion-targeted biopsy between January 2014 and February 2016. Suspicious lesions were delineated using a 'region of interest' and the system calculated prostate volume and LV. Patients were divided in groups considering LV (≤0.5, 0.5-1, ≥1 mL) and PI-RADS score (1-5). We considered clinically significant prostate cancer as all cancers with a Gleason score of ≥3 + 4 as suggested by PI-RADS v2. A direct comparison between MRI estimated LV (MRI LV) and histological tumour volume (HTV) was done in 23 patients who underwent radical prostatectomy during the study period. Differences between MRI LV and HTV were assessed using the paired sample t-test. MRI LV and HTV concordance was verified using a Bland-Altman plot. The chi-squared test and logistic and ordinal regression models were used to evaluate difference in frequencies. RESULTS: The MRI LV and PI-RADS score were associated both with prostate cancer detection (both P < 0.001) and with significant prostate cancer detection (P < 0.001 and P = 0.008, respectively). When the two variables were matched, increasing LV increased the risk within each PI-RADS group. Prostate cancer detection was 1.4-times higher for LVs of 0.5-1 mL and 1.8-times higher for LVs of ≥1 mL; significant prostate cancer detection was 2.6-times for LVs of 0.5-1 mL and 4-times for LVs of ≥1 mL. There was a positive correlation between MRI LV and HTV (r = 0.9876, P < 0.001). Finally, Bland-Altman analysis showed that MRI LV was underestimated by 4.2% compared to HTV. Study limitations include its monocentric and retrospective design and the limited cohort. CONCLUSIONS: This study demonstrates that PI-RADS score and the MRI LV, independently and in combination, are associated with prostate cancer detection and with tumour clinical significance.

QTc interval in patients with multiple sclerosis: an inference from the insula of Reil?

BACKGROUND AND PURPOSE: The aim of this study was to investigate the correlation between the duration of the QTc interval and the brain lesion load at the level of the structures involved in superior autonomic control (insula, cingulate cortex and amygdala-hippocampus) in multiple sclerosis (MS) patients. METHODS: Thirty-one consecutive patients with relapsing-remitting MS were recruited. The QT interval was measured manually in all 12 leads by a single blinded observer, with the longest QT value adjusted for heart rate by using the Bazett's formula. All patients performed a brain magnetic resonance imaging (MRI) scan including three-dimensional double inversion recovery and three volumetric fast-field echo sequences. The following MRI measures were obtained: (i) global and regional cortical thickness (CTh); (ii) white matter lesion load volume; (iii) cortical damage blindly assessed by a trained observer who assigned, on the basis of the number of cortical lesions, a score from 0 to 5 for each of the brain areas analysed. RESULTS: In all, 16% of the patients had an increased QTc interval. The QTc interval was correlated with disease duration, cortical insular lesion volume and grey matter lesion volume in the three examined areas and inversely correlated with global and insular CTh. CONCLUSIONS: An increased QTc interval in patients with MS may have a cerebral origin possibly driven by involvement of the insular cortex. With the recent introduction in clinical practice of treatments with potential cardiac effects such as fingolimod, the recognition of a long QTc interval could be clinically crucial and should encourage appropriate electrocardiographic monitoring in order to prevent the risk of malignant ventricular pro-arrhythmia and iatrogenic sudden death.

Perinatal features of congenital cystic lung diseases: results of a nationwide multicentric study in Japan.

PURPOSE: The current study aimed to assess the perinatal risk and clinical features of congenital cystic lung diseases (CCLD). MATERIALS AND METHODS: Of the 874 CCLD patients identified in a nationwide survey, 428 patients born between 1992 and 2012 and treated at 10 high-volume centers, were retrospectively reviewed. RESULTS: Fetal hydrops was visualized using MRI in 9.2 % of the patients. Prenatal interventions were described for 221 of the 428 patients, including the maternal administration of steroid and pleuro-amniotic shunting. Postnatally, a right-to-left shunt flow through a persistent ductus arteriosus was observed in 7.8 % of the patients. The fetal lung lesion volume ratio (LVR) was significantly higher among these symptomatic patients (2.04 ± 1.71 vs. 0.98 ± 0.50, P < 0.00071), and decreased to a greater degree in non-CCAM patients compared with CCAM patients during the late gestational period (from 1.37 ± 1.28 to 1.14 ± 0.84 in CCAM and from 1.08 ± 0.47 to 0.46 ± 0.64 in non-CCAM). CONCLUSIONS: An estimated 8-9 % of prenatally diagnosed patients carry the highest risk of perinatal respiratory distress. Fetal LVR remaining at a high level during the late gestational period seems to predict a high risk.