Contribution of magnetic resonance spectrometry to the diagnosis of intracranial tumors

Magnetic resonance spectroscopy (MRS) is a method enabling the analysis of the tissue metabolic content. It may offer a more accurate diagnosis of the intracranial tumors than conventional MRI sequences. MRS of normal brain parenchyma displays 4 main metabolites: N-acetyl aspartate (neuronal marker), creatine (cellular density marker), choline (membrane activity marker) and myoinositol (glial marker); pathological processes lead to variations of the level of these metabolites and/or the appearance of abnormal metabolites (lactate), following different patterns according to pathological process involved: glioma, meningioma, metastasis, bacterial or toxoplasmic abscess, radionecrosis. The potential clinical use of this method includes positive, differential and etiological diagnosis of tumors, determination of the level of malignancy of gliomas, screening for tumor recurrence following treatment. Our laboratory has been performing MR spectroscopic explorations of brain tumors for many years. Based on this experience, we show how MRS can be routinely performed in the clinical setting, what are its limitations and potential, and what kind of information can be supplied to the clinician.     

Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis

PURPOSE: To determine whether voxel-based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS). MATERIALS AND METHODS: We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test (P <0.0001, k=20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. RESULTS: A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. CONCLUSION: These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease.     

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms

A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms.     

Improving diagnosis accuracy of brain volume abnormalities during childhood with an automated MP2RAGE-based MRI brain segmentation

Background and purposeIt can be challenging to depict brain volume abnormalities in the pediatric population on magnetic resonance imaging (MRI). The aim of the study was to evaluate the inter-radiologist reliability in brain MRI interpretation, including brain volume assessment and the efficiency of an automated brain segmentation.Materials and methodsWe performed a single-center prospective study including 44 patients aged six months to five years recruited from the University Hospital, having a 1.5 T brain MRI using a MP2RAGE sequence. All MRI were randomly and blindly reviewed by one junior and two senior pediatric radiologists. Inter-observer agreements were assessed using Fleiss’ kappa coefficient. Brain volumetry (total intracranial volume (TIV), brain parenchyma, and cerebrospinal fluid volumes) was estimated using the MorphoBox prototype. Clinical head circumference (HC) and z scores were reported. A Pearson correlation coefficient was calculated between brain volumes with HC.ResultsTwenty-four brain MRI examinations were normal and twenty were pathological. Brain volume abnormalities were poorly detected by junior and senior radiologists: sensitivities 16.67% [confidence interval 4.7–44.8], 33.33% [13–60] and 30.7% [12–58] and specificities 93.75% [79–98], 84.38% [68–93] and 77% [60–88], respectively. Brain volume apart, interobserver kappa coefficients were 0.93 between junior and seniors as well as between seniors. Brain volumes were significantly correlated with HC (P < 0.0001). In patients with normal MRI, brain parenchyma volumes increased regularly with age. Low brain volume was easier to identify with automated quantification.ConclusionBrain volume was poorly appreciated by radiologists. The fully automated brain segmentation used can provide quantitative data to better diagnose, describe, and follow-up brain volume abnormalities.     

Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse

Behaviour was assessed in 32 C57BL/6JCrl and 32 C3H/HeN male mice 1 h following vasectomy; saline or meloxicam was administered 30 min prior to surgery at 5, 10, or 20 mg kg(-1). Faeces were collected 24 h prior to, and 3, 6, 9, 12, 24 h following, vasectomy for measurement of faecal corticosterone. Peak corticosterone levels were significantly higher in mice that underwent vasectomy and received saline (p<0.001) or meloxicam at 5 or 10 mg kg(-1) (p=0.021, and p<0.001, respectively) compared with normal un-operated controls. Mice that underwent vasectomy and received 20 mg kg(-1) meloxicam had peak corticosterone levels that were not different from normal un-operated mice (p=0.254). Discriminant analysis was used to identify behaviours responsible for group separation; these were summed to create two behaviour scores. Score 2 (the frequency of flinching, writhing, rear leg lift and press 2) was thought to be pain related; mice that underwent vasectomy and received saline exhibited significantly more of these behaviours than the normal controls (p=0.032), and the mice that received meloxicam (at any dose). Strain differences were observed in both the stress response to vasectomy and the behavioural changes; the C3H/HeN mice had higher pain scores (behaviour Score 2) and peak corticosterone responses than the C57BL/6JCrl mice. We have demonstrated that significant changes occur in the behaviour of mice following vasectomy, and these changes are reduced by use of meloxicam. Vasectomy elicits a rise in corticosterone levels that was only reduced by the highest dose of meloxicam.     

Bacteremia caused by a metronidazole-resistant Prevotella sp. strain

Metronidazole resistance among Prevotella spp. is rare. We report here the first case of bacteremia due to a high-level metronidazole-resistant Prevotella sp. responsible for treatment failure.     

Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA

We reported that RNA condensed on protamine is protected from RNase-mediated degradation and can be used for vaccination. Here, we show that such complexes are also danger signals that activate mouse cells through a MyD88-dependent pathway. Moreover, mRNA-protamine complexes stimulate human blood cells. They strongly activate DC and monocytes, leading to TNF-alpha and IFN-alpha secretion. In addition, protamine-RNA complexes directly activate B cells, NK cells and granulocytes. The detailed analysis of the activated cell types, the study of the cytokines released from PBMC cultured with protamine-RNA complexes and recently published results suggest that TLR-7 and TLR-8 may be involved in the recognition of protamine-stabilized RNA. Our data indicate that protamine-stabilized RNA, which may be similar to RNA condensed in the nucleocapsids of RNA viruses, is a strong danger signal. Thus, similarly to plasmid DNA, protamine-RNA combines antigen production and non-specific immunostimulation. The studies presented here explain the capacity of protamine-RNA to act as a vaccine, and pave the way towards the development of safe and efficient mRNA-based immunotherapies.     

Inactivation of p16 INK4a /CDKN2A gene may be a diagnostic feature of large B cell lymphoma leg type among cutaneous B cell lymphomas

The World Health Organization-European Organization for Research and Treatment of Cancer has individualized three main categories among the primary cutaneous B cell lymphoma (PCBCL): leg-type primary cutaneous large B cell lymphoma (PCLBCL leg type), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous marginal zone lymphoma (PCMZL). The genetic features of 21 PCBCL cases (six PCLBCL leg type four PCFCL large cells, seven PCFCL small cells, and four PCMZL) were investigated by comparative genomic hybridization (CGH array). Fluorescent in situ hybridization (FISH) analysis was performed to confirm CGH array data and to detect lymphoma-associated gene rearrangements. p14 ( ARF )/p16 ( INK4a ) CDKN2A gene quantification, methylation analysis, and immunohistochemical detection were also performed. CGH array showed a higher number of recurrent genetic imbalances in PCLBCL leg type (mean 62) than in PCFCL large cells (mean 34). PCFCL small cells and PCMZL exhibited fewer chromosomal alterations (mean 24 and 9). FISH analysis provided concordant results with CGH array data in 97% (98 of 101) assays and demonstrated a t(8;14)(q24;q32) in two of six PCLBCL leg type. Recurrent deletions in 9p21 (p14 ( ARF )/p16 ( INK4a ) CDKN2A) were a constant finding in PCLBCL leg type (six of six). Conversely, PCFCL large cells exhibited recurrent 1p36 deletions (four of four) without deletion in 9p21 (zero of four). The diagnostic and prognostic impact of the p16 ( INK4a ) CDKN2A gene status in PCBCL should therefore be confirmed on a larger series.     

Purification and partial characterization of a 32-kilodalton sialic acid-specific lectin from Aspergillus fumigatus

Adherence of the opportunistic fungus Aspergillus fumigatus to the extracellular matrix components is considered a crucial step in the establishment of the infection. Given the high carbohydrate content of these glycoproteins and the role of carbohydrate-protein interactions in numerous adherence processes, the presence of a lectin in A. fumigatus was investigated. Different fungal extracts obtained by sonication or grinding in liquid nitrogen from resting or swollen conidia, as well as from germ tubes and mycelium, were tested by hemagglutination assays using rabbit erythrocytes. A lectin activity was recovered in all the extracts tested. However, sonication of resting conidia resulted in the highest specific activity. Purification of the lectin was achieved by gel filtration followed by ion-exchange and hydrophobic-interaction chromatographies. Analysis of the purified lectin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed an apparent molecular mass of 32 kDa, which is similar to that of the alkaline protease already identified from different strains of A. fumigatus. However, as evidenced by the use of an alkaline protease-deficient mutant, the two activities were supported by distinct proteins. In addition, hemagglutination inhibition experiments using different saccharides and glycoproteins demonstrated the specificity of the lectin for sialic acid residues. Together these results suggest that this lectin may contribute to the attachment of conidia to the extracellular matrix components through the recognition of the numerous terminal sialic acid residues of their carbohydrate chains.