Evaluation of proton density fat fraction (PDFF) obtained from a vendor-neutral MRI sequence and MRQuantif software.

OBJECTIVE: To validate the proton density fat fraction (PDFF) obtained by the MRQuantif software from 2D chemical shift encoded MR (CSE-MR) data in comparison with the histological steatosis data. METHODS: This study, pooling data from 3 prospective studies spread over time between January 2007 and July 2020, analyzed 445 patients who underwent 2D CSE-MR and liver biopsy. MR derived liver iron concentration (MR-LIC) and PDFF was calculated using the MRQuantif software. The histological standard steatosis score (SS) served as reference. In order to get a value more comparable to PDFF, histomorphometry fat fraction (HFF) were centrally determined for 281 patients. Spearman correlation and the Bland and Altman method were used for comparison. RESULTS: Strong correlations were found between PDFF and SS (rs = 0.84, p < 0.001) or HFF (rs = 0.87, p < 0.001). Spearman's coefficients increased to 0.88 (n = 324) and 0.94 (n = 202) when selecting only the patients without liver iron overload. The Bland and Altman analysis between PDFF and HFF found a mean bias of 5.4% ± 5.7 [95% CI 4.7, 6.1]. The mean bias was 4.7% ± 3.7 [95% CI 4.2, 5.3] and 7.1% ± 8.8 [95% CI 5.2, 9.0] for the patients without and with liver iron overload, respectively. CONCLUSION: The PDFF obtained by MRQuantif from a 2D CSE-MR sequence is highly correlated with the steatosis score and very close to the fat fraction estimated by histomorphometry. Liver iron overload reduced the performance of steatosis quantification and joint quantification is recommended. This device-independent method can be particularly useful for multicenter studies. CLINICAL RELEVANCE STATEMENT: The quantification of liver steatosis using a vendor-neutral 2D chemical-shift MR sequence, processed by MRQuantif, is well correlated to steatosis score and histomorphometric fat fraction obtained from biopsy, whatever the magnetic field and the MR device used. KEY POINTS: • The PDFF measured by MRQuantif from 2D CSE-MR sequence data is highly correlated to hepatic steatosis. • Steatosis quantification performance is reduced in case of significant hepatic iron overload. • This vendor-neutral method may allow consistent estimation of PDFF in multicenter studies.

Multimodal MRI cerebral correlates of verbal fluency switching and its impairment in women with depression.

BACKGROUND: The search of biomarkers in the field of depression requires easy implementable tests that are biologically rooted. Qualitative analysis of verbal fluency tests (VFT) are good candidates, but its cerebral correlates are unknown. METHODS: We collected qualitative semantic and phonemic VFT scores along with grey and white matter anatomical MRI of depressed (n = 26) and healthy controls (HC, n = 25) women. Qualitative VFT variables are the "clustering score" (i.e. the ability to produce words within subcategories) and the "switching score" (i.e. the ability to switch between clusters). The clustering and switching scores were automatically calculated using a data-driven approach. Brain measures were cortical thickness (CT) and fractional anisotropy (FA). We tested for associations between CT, FA and qualitative VFT variables within each group. RESULTS: Patients had reduced switching VFT scores compared to HC. Thicker cortex was associated with better switching score in semantic VFT bilaterally in the frontal (superior, rostral middle and inferior gyri), parietal (inferior parietal lobule including the supramarginal gyri), temporal (transverse and fusiform gyri) and occipital (lingual gyri) lobes in the depressed group. Positive association between FA and the switching score in semantic VFT was retrieved in depressed patients within the corpus callosum, right inferior fronto-occipital fasciculus, right superior longitudinal fasciculus extending to the anterior thalamic radiation (all p < 0.05, corrected). CONCLUSION: Together, these results suggest that automatic qualitative VFT scores are associated with brain anatomy and reinforce its potential use as a surrogate for depression cerebral bases.

Prognostic value of spinal cord MRI in multiple sclerosis patients.

Multiple sclerosis [MS] is a common inflammatory, demyelinating and neurodegenerative disease of the central nervous system that affects both the brain and the spinal cord. In clinical practice, spinal cord MRI is performed far less frequently than brain MRI, mainly owing to technical limitations and time constraints. However, improvements of acquisition techniques, combined with a strong diagnosis and prognostic value, suggest an increasing use of spinal cord MRI in the near future. This review summarizes the current data from the literature on the prognostic value of spinal cord MRI in MS patients in the early and later stages of their disease. Both conventional and quantitative MRI techniques are discussed. The prognostic value of spinal cord lesions is clearly established at the onset of disease, underlining the interest of spinal cord conventional MRI at this stage. However, studies are currently lacking to affirm the prognostic role of spinal cord lesions later in the disease, and therefore the added value of regular follow-up with spinal cord MRI in addition to brain MRI. Besides, spinal cord atrophy, as measured by the loss of cervical spinal cord area, is also associated with disability progression, independently of other clinical and MRI factors including spinal cord lesions. Although potentially interesting, this measurement is not currently performed as a routine clinical procedure. Finally, other measures extracted from quantitative MRI have been established as valuable for a better understanding of the physiopathology of MS, but still remain a field of research.

Exposure of pregnant women to organophosphate insecticides and child motor inhibition at the age of 10-12 years evaluated by fMRI.

BACKGROUND: Organophosphate pesticides (OP) are widely used for both agricultural and domestic purposes. Epidemiological studies suggest neurotoxicity in children after exposure to organophosphates pesticides (OP) at low levels but possible mechanism is still unclear. OBJECTIVES: We aimed at investigating the effects of prenatal exposure to OPs on inhibitory control of 10-12 year-old-children assessed by a motor inhibition task during functional magnetic resonance imaging (fMRI). METHODS: Ninety-five children from the PELAGIE cohort (Brittany-France, from 2002) underwent a fMRI examination during which inhibition was assessed by a Go/No-Go task. Task performance was assessed by average response latency, commission rate and composite performance score (PS). Whole brain activation was estimated by modeling the hemodynamic response related to inhibition demand and successful inhibition. OP exposure was assessed by measuring six dialkylphosphate (DAP) metabolites in the urine of women in early pregnancy (<19 WG). Concentrations were summed to obtain overall levels of diethylphosphate (DE), dimethylphosphate (DM) and total non-specific metabolites (DAP), standardized to homogenize sampling conditions and categorized into levels of exposure: low (reference), moderate or high. Regression models were adjusted for potential cofounders considered by restriction and statistical criteria. RESULTS: Moderate levels of DAP were associated with a decreased commission rate (ß = -6.65%, p = 0.04), indicating improved performance. Increasing levels of DM and DE were associated with decreased brain activity in the left inferior and bilateral superior frontal regions during successful inhibition. We did not observe any differential activation related to inhibitory demands. DISCUSSION: These results suggest that prenatal OPs may be associated with altered pattern of brain activity in regions related to inhibition among children and need to be confirmed by additional studies.

Assessment of liver iron overload by 3 T MRI.

PURPOSE: To evaluate the performance and limitations of the signal intensity ratio method for quantifying liver iron overload at 3 T. METHODS: Institutional review board approval and written informed consent from all participants were obtained. One hundred and five patients were included prospectively. All patients underwent a liver biopsy with biochemical assessment of hepatic iron concentration and a 3 T MRI scan with 5 breath-hold single-echo gradient-echo sequences. Linear correlation between liver-to-muscle signal intensity ratio and liver iron concentration was calculated. The algorithm for calculating magnetic resonance hepatic iron concentration was adapted from the method described by Gandon et al. with echo times divided by 2. Sensitivity and specificity were calculated. RESULTS: Five patients were excluded (coil selection failure or missing sequence) and 100 patients were analyzed, 64 men and 36 women, 52 ± 13.3 years old, with a biochemical hepatic iron concentration range of 0-630 µmol/g. Linear correlation between biochemical hepatic iron concentration and MR-hepatic iron concentration was excellent with a correlation coefficient = 0.96, p < 0.0001. Sensitivity and specificity were, respectively, 83% (0.70-0.92) and 96% (0.85-0.99), with a pathological threshold of 36 µmol/g. CONCLUSION: Signal intensity ratio method for quantifying liver iron overload can be used at 3 T with echo times divided by 2.

Arterial spin labeling (ASL) perfusion: techniques and clinical use.

Arterial spin labeling (ASL) perfusion is a MRI technique to quantify tissue blood flow. ASL is a non-invasive technique that labels the protons in the arterial blood by radiofrequency pulses, without the exogenous injection of contrast media. This article has three goals: 1) present the principles of ASL perfusion, the types of labeling and the ways to obtain the mapping; 2) specify and the quality criteria for the mapping obtained, while emphasizing the artifacts; and 3) describe the main encephalic and renal applications.

Non-ECG-gated unenhanced MRA of the carotids: optimization and clinical feasibility.

OBJECTIVES: To optimise and assess the clinical feasibility of a carotid non-ECG-gated unenhanced MRA sequence. METHODS: Sixteen healthy volunteers and 11 patients presenting with internal carotid artery (ICA) disease underwent large field-of-view balanced steady-state free precession (bSSFP) unenhanced MRA at 3T. Sampling schemes acquiring the k-space centre either early (kCE) or late (kCL) in the acquisition window were evaluated. Signal and image quality was scored in comparison to ECG-gated kCE unenhanced MRA and TOF. For patients, computed tomography angiography was used as the reference. RESULTS: In volunteers, kCE sampling yielded higher image quality than kCL and TOF, with fewer flow artefacts and improved signal homogeneity. kCE unenhanced MRA image quality was higher without ECG-gating. Arterial signal and artery/vein contrast were higher with both bSSFP sampling schemes than with TOF. The kCE sequence allowed correct quantification of ten significant stenoses, and it facilitated the identification of an infrapetrous dysplasia, which was outside of the TOF imaging coverage. CONCLUSIONS: Non-ECG-gated bSSFP carotid imaging offers high-quality images and is a promising sequence for carotid disease diagnosis in a short acquisition time with high spatial resolution and a large field of view. KEY POINTS: • Non-ECG-gated unenhanced bSSFP MRA offers high-quality imaging of the carotid arteries. • Sequences using early acquisition of the k-space centre achieve higher image quality. • Non-ECG-gated unenhanced bSSFP MRA allows quantification of significant carotid stenosis. • Short MR acquisition times and ungated sequences are helpful in clinical practice. • High 3D spatial resolution and a large field of view improve diagnostic performance.

[Innovations in functional MR imaging of the brain: arterial spin labeling and diffusion]. / Innovations en IRM fonctionnelle cérébrale : marquage de spins artériels et diffusion.

The standard technique for brain activation functional MRI (fMRI) is the BOLD sequence. Two new techniques have emerged: arterial spin labeling (ASL) MRI and diffusion MRI. Both have the theoretical advantage of more accurately directly demonstrating neuronal activation compared to BOLD imaging, resulting in improved spatial and temporal resolution. ASL is a perfusion sequence using labeled arterial protons as an endogenous perfusion agent. In spite of methodological difficulties, quantitative CBF measurements are possible. ASL is less susceptible to venous contamination than BOLD and more reproducible. Diffusion MRI evaluates neuronal activation at the cellular level with the prospect of excellent spatial resolution. The main limitations for both techniques are the technical difficulties in the acquisition and the low SNR. AS such, ASL is not widely used clinically and diffusion remains in the field of research. However, the increasing availability of 3T MR systems coupled with multi-channel surface coils and improved postprocessing techniques should improve the detection of the brain activation signal. It is thus possible that these techniques could become clinically available either in complement to or as a replacement for BOLD imaging.

Malnourished elderly people and lipid status.

UNLABELLED: Protein-energy malnutrition is common in the elderly. The relationship between protein-energy malnutrition and lipid status remains uncertain and few studies are available. The aim of this study was to evaluate the lipid status of malnourished elderly subjects recently hospitalized in a geriatric medical care unit. Classical parameters such as total cholesterol, HDL cholesterol, apoproteins A1 et B, vitamins A and E were measured. Particular attention was given to other parameters such as fatty acids. The studied population included 86 elderly subjects. They were divided into two groups, according to serum albumin (alb) and Body Mass Index (BMI). Fifty patients aged 81.5 7.3 years were considered to be well-nourished (WN) with albumin 35 g/l and BMI 21 kg/m2. Thirty six patients aged 84.1 6.6 years were considered to be malnourished (MN) with albumin < 35 g/l and BMI < 21 kg/m2. Our main findings shown significant decrease in all classical lipid parameters : total cholesterol (p< 0.001), HDL cholesterol (p< 0.005), apoproteins A1 (p< 0.001) and B (p< 0.001) in the malnourished group. We found an increase in the rate of v9 fatty acids (p< 0.001 for the oleic acid; p< 0.05 for the eicosatrienoic acid) and also an increase in the triene/tetraene ratio (p< 0.05) as a result of malnutrition. CONCLUSION: Protein-energy malnutrition is accompanied by lipid status alterations.

Specific changes in n -6 fatty acid metabolism in patients with chronic intestinal failure.

BACKGROUND AND AIMS: In patients presenting severe malabsorption, essential fatty acid (EFA) deficiency can be corrected by intravenous lipids, but EFA abnormalities persist. The purpose of this study was to evaluate the role of large resection of the small bowel or malabsorption on plasma phospholipid EFA profile. METHODS: The plasma phospholipid EFA composition was measured by gas chromatography in home parenteral nutrition patients with (n=13) or without small bowel resection (n=7) and in 14 healthy subjects. RESULTS: The two groups of patients had the same nutritional status and comparable amounts of intravenous fat. In both groups, plasma fatty acid concentrations were significantly different from those observed in healthy subjects without EFA deficiency. Among them: a decrease in 18:2n -6, 22:5n -3, 22:6n -3 and an increase in 18:3n -3, 20:4n -6, 22:4n -6. Moreover, arachidonic acid to linoleic acid ratio was higher in both groups of patients, suggesting a stimulation of the elongation and desaturation of 18:2n -6. In multiple linear regression, 18:2n -6 and 20:4n -6 levels were not associated with the small bowel length, only 22:6n -3 concentration was correlated with small bowel length. CONCLUSIONS: The patients with chronic intestinal failure on home parenteral nutrition presented specific change in their EFA and an increase in the n -6 fatty acid pathway. This could be related to the severe malabsorption.

Oxidants and antioxidants in long-term haemodialysis patients.

Survival for decades is now possible in end-stage renal disease patients (ESRD) treated with haemodialysis (HD). Long-term survivors may present dialysis-related pathology (DRP). Alterations in lipid metabolism and oxidative stress are recognized as important risk factors that could be prevented or reduced by optimal therapy. We have studied markers of oxidative stress in patients receiving HD treatment for more than 20 years. In order to evaluate a preventive intervention against oxidative damage we measured the factors implied for the prooxidative and antioxidative mechanisms in haemodialysis patients. Ten long-term HD survivors (HD duration: 274.2 months) and ten patients with recent onset of HD (HD duration: 17.8 months), had blood drawn for plasma vitamins A and E, malondialdehyde (MDA), plasma and RBC glutathione peroxidase (GPx), RBC superoxide dismutase (SOD), plasma and erythrocyte glutathione reductase (GSSG-R), oxidized and reduced glutathione (GSH) assessment. Despite normal levels of antioxidant vitamins, an usual finding in this setting, increased MDA, and oxidized GSH, and decreased plasma GPx and reduced GSH show that oxidant stress is markedly present in both recent onset and long-term HD patients. It would appear highly advantageous to reduce complications of long-term dialysis patients with preventing modalities.

Low-density lipoprotein (LDL) behavior after in vitro oxidation in three groups of diabetics.

Diabetes is associated with increased morbidity and mortality resulting from cardiovascular disease. It has been established that oxidized LDLs are involved in the genesis of atherosclerosis. We have studied LDL oxidizability in three types of diabetics: insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) and insulin-treated diabetes mellitus type 2 (ITDM2) and a control group. LDLs have been isolated using ultracentrifugation and oxidized by addition of cupric chloride. With the oxidation kinetic, we calculated the lag time and the oxidation rate. Total fatty acids, alpha-tocopherol, and malondialdehyde (MDA) have been measured in native and oxidized LDLs. Diabetics have a significantly lower lag time and a lower level of alpha-tocopherol. Oxidized LDLs of diabetics show an important decrease of their polyunsaturated fatty acids with an increase of MDA compared to the control. Our study demonstrates a higher susceptibility to oxidation of LDL from diabetics; this can be explained by alteration in LDL composition or by the oxidative process occurring in this disease.

Quantitation of reduced and total glutathione at the femtomole level by high-performance liquid chromatography with fluorescence detection: application to red blood cells and cultured fibroblasts.

A new rapid and highly sensitive HPLC method with ortho-phthalaldehyde (OPA) pre-column derivatization has been developed for determination of reduced glutathione (GSH) and total glutathione (GSHt) in human red blood cells and cultured fibroblasts. OPA derivatives are separated on a reversed-phase HPLC column with an acetonitrile-sodium acetate gradient system and detected fluorimetrically. An internal standard (glutathione ethyl ester) is added to facilitate quantitation. Total glutathione is determined after reduction of disulfide groups with dithiothreitol; the oxidized glutathione (GSSG) concentration is calculated by subtraction of the GSH level from the GSHt level. The assay shows high sensitivity (50 fmol per injection, the lowest reported), good precision (C.V. <5.0%), an analytical recovery of GSH and GSSG close to 100%, and linearity (r > 0.999). This HPLC technique is very simple and rapid. Its wide applicability and high sensitivity make it a convenient and reliable method for glutathione determination in various biological samples.

[Multiplication of chromosomes and primary leucocyte number in childhood ALL and hyperdiploid karyotype]. / Chromosomenvervielfachung und primäre Leukozytenzahl bei Kindern mit einer ALL und hyperdiploidem Chromosomensatz.

In the blast cells of children with acute lymphoblastic leukemia (ALL) more than 50 chromosomes can be observed in a quarter of cases. As a rule these children have a good prognosis. However, some of these patients develop a relapse of their basic disease. There is only poor information about the significance of distinct additional chromosomes for the prognosis. The white blood cell count (WBC) at the time of diagnosis is a further very important prognostic factor in childhood ALL. Therefore we compared the relation between trisomy of distinct chromosomes and the initial white blood cell count of 41 children with common ALL and hyperdiploid karyotype. The modal chromosome number ranged from 50 to 60 chromosomes. Most frequently, the chromosomes X, 4, 6, 8, 10, 17, 18 and 21 were multiplied. Additionally, in 25 of the 41 cases structural chromosome aberrations were observed. The average WBC was estimated as 9.6 Gpt/l with a range from 1.8 to 41.5 Gpt/l. The initial WBC was slightly increased in patients with the additional chromosome X, 6, 11, 12 or 19 and distinctly decreased in children with the additional chromosome 8 or 9 in their hyperdiploid blast cells. No patient with an additional Chromosome 9 showed a WBC higher than 10 Gpt/l and only 2 out of the 12 children with an additional chromosome 8 revealed an initial WBC higher than 10 Gpt/l. Additional structural chromosome aberrations were without influence on the WBC.

[Multicenter evaluation of thr Abbott glycosylated hemoglobin assay on IMx]. / Evaluation multicentrique de test Abbott hémoglobine glyquée sur IMx.

The Abbott IMx glycated hemoglobin assay was evaluated in a multicentre study. This method utilizes boronate affinity chromatography, and ion-capture technology. This assay determines both total glycohemoglobin (% GHb) and percentage of hemoglobin Alc (% HbAlc). The precision of the assay was evaluated: the intra-assay and interassay coefficients of variation were judged to be satisfactory (< 6.5%). We determined the accuracy of the assay by comparison with a reference HPLC assay for 603 specimens; coefficients of correlation were between 0.88 and 0.96. We studied the interference of bilirubin and glucose and found no interference at usual concentrations. The presence of abnormal hemoglobins (HbF and some Hb structural variants HbS, HbC) was not detected with the Abbott IMx assay; however, this assay showed no significant interference from the hemoglobin variants tested for heterozygous hemoglobinopathies (percentage of abnormal hemoglobin < 60%). We also determined normal values for HbAlc with this technology (164 specimens): 4.1 to 6.1%.

The translocation t(1;22)(p13;q13) is a nonrandom marker specifically associated with acute megakaryocytic leukemia in young children.

We present the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;22)(p13;q13) in children with acute nonlymphocytic leukemia (ANLL). This karyotype anomaly occurred in leukemia cells from five of 445 (1.1%) children with newly diagnosed ANLL who were successfully studied by cytogenetic analysis at four European centers between January 1987 and January 1992. The occurrence of the t(1;22) was restricted to the French-American-British classification (FAB) subtype M7. The overall incidence in children with acute megakaryocytic leukemia (AMKL) was 27.8% (5/18 cases); in infants with AMKL, the frequency of the t(1;22) was 66.7% (4/6 cases). Three of the patients carrying this anomaly had a diploid karyotype, whereas in two cases a hyperdiploid karyotype was found. However, in all five patients, the t(1;22) was the only translocation event present at diagnosis. All patients received aggressive chemotherapy for acute myelogenous leukemia (AML). Two patients died within 15 months of diagnosis without entering remission. One of three patients who entered remission died 7 months after diagnosis, most likely from intramedullar hemorrhage. Only two of the five children with the t(1;22) who received autologous bone marrow transplantation (BMT) are alive and in complete remission (CR) 23 and 40 months after diagnosis, respectively. At the time of diagnosis, the age of the oldest child carrying the t(1;22) was 18 months. The cases with this chromosome anomaly were compared with an age-matched group of five children with AMKL lacking this translocation. The patients with the t(1;22) had a lower median value of the peripheral white blood cell (WBC) count and a higher median hemoglobin level than the patients from the matched group. In the latter cases, normocellular or hypercellular bone marrow (BM) was detected at diagnosis. In contrast, all children with the t(1;22) in our series had a hypocellular BM. Histological BM analyses were available in three of these patients and showed marked fibrosis. Other clinical and laboratory parameters showed no obvious differences between the matched groups. Despite intensive chemotherapy, AMKL in children appears to be associated with a poor prognosis. The clinical courses of the children with AMKL and the t(1;22) presented may be indicative of a beneficial effect of autologous BMT in this subset of patients.