Noise correlations and SNR in phased‐array MRS

The acquisition of magnetic resonance spectroscopy (MRS) signals by multiple receiver coils can improve the signal‐to‐noise ratio (SNR) or alternatively can reduce the scan time maintaining a reliable SNR. However, using phased array coils in MRS studies requires efficient data processing and data combination techniques in order to exploit the sensitivity improvement of the phased array coil acquisition method. This paper describes a novel method for the combination of MRS signals acquired by phased array coils, even in presence of correlated noise between the acquisition channels. In fact, although it has been shown that electric and magnetic coupling mechanisms produce correlated noise in the coils, previous algorithms developed for MRS data combination have ignored this effect. The proposed approach takes advantage of a noise decorrelation stage to maximize the SNR of the combined spectra. In particular Principal Component Analysis (PCA) was exploited to project the acquired spectra in a subspace where the noise vectors are orthogonal. In this subspace the SNR weighting method will provide the optimal overall SNR. Performance evaluation of the proposed method is carried out on simulated ¹H‐MRS signals and experimental results are obtained on phantom ¹H‐MR spectra using a commercially available 8‐element phased array coil. Noise correlations between elements were generally low due to the optimal coil design, leading to a fair SNR gain (about 0.5%) in the center of the field of view (FOV). A greater SNR improvement was found in the peripheral FOV regions. Copyright © 2009 John Wiley & Sons, Ltd.     

A deoxyribonucleotidase in mitochondria: involvement in regulation of dNTP pools and possible link to genetic disease

Three cytosolic and one plasma membrane-bound 5'-nucleotidases have been cloned and characterized. Their various substrate specificities suggest widely different functions in nucleotide metabolism. We now describe a 5'-nucleotidase in mitochondria. The enzyme, named dNT-2, dephosphorylates specifically the 5'- and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The cDNA of human dNT-2 codes for a 25.9-kDa polypeptide with a typical mitochondrial leader peptide, providing the structural basis for two-step processing during import into the mitochondrial matrix. The deduced amino acid sequence is 52% identical to that of a recently described cytosolic deoxyribonucleotidase (dNT-1). The two enzymes share many catalytic properties, but dNT-2 shows a narrower substrate specificity. Mitochondrial localization of dNT-2 was demonstrated by the mitochondrial fluorescence of 293 cells expressing a dNT-2-green fluorescent protein (GFP) fusion protein. 293 cells expressing fusion proteins without leader peptide or with dNT-1 showed a cytosolic fluorescence. During in vitro import into mitochondria, the preprotein lost the leader peptide. We suggest that dNT-2 protects mitochondrial DNA replication from overproduction of dTTP, in particular in resting cells. Mitochondrial toxicity of dTTP can be inferred from a severe inborn error of metabolism in which the loss of thymidine phosphorylase led to dTTP accumulation and aberrant mitochondrial DNA replication. We localized the gene for dNT-2 on chromosome 17p11.2 in the Smith-Magenis syndrome-critical region, raising the possibility that dNT-2 is involved in the etiology of this genetic disease.     

Pulmonary hypertension in sickle cell disease children under 10 years of age

Despite the finding of elevated Tricuspid Regurgitant Velocity (TRV) in children below 5 years of age, the prevalence and evolution of Pulmonary Hypertension ( PH ) in young children with sickle cell disease ( SCD ) are unclear. In order to identify predictive factors of precocious PH development, SCD children ≥3 years old, at steady state, underwent annual echocardiography and Tissue Doppler Imaging (TDI). Patients receiving chronic transfusion were excluded. Thirty‐seven of seventy‐five patients were ≥3 years, with measurable TRV. In our young population (mean age 6·2 years) of mainly African, HbS/HbS patients, 8/37 (21·6%) had TRV ≥2·5 m/s, 8% being only 3 years old. Significant correlation was found between precocious TRV elevation and high platelet and reticulocyte counts and frequent acute chest syndromes (ACS). In multivariate analysis, ACS was the only variable predicting TRV ≥2·5 m/s. TDI of the 37 patients showed signs of diastolic dysfunction of the left ventricle. At follow‐up all eight patients with high TRV displayed further increase and seven more developed TRV ≥2·5 m/s. PH seems to begin in children earlier than expected. Factors involved in its early onset might be different from the ones causing its development in older children or adults. African children might benefit from early screening and re‐assessment once a year.     

Electrocardiographic abnormalities in infants born from mothers with autoimmune diseases--a multicentre prospective study

OBJECTIVES: To assess the prevalence of congenital heart block (CHB) and electrocardiographic (ECG) abnormalities in infants of anti-Ro/SSA-positive women. METHODS: Sixty anti-Ro-positive and 36 anti-Ro-negative patients were prospectively followed before/during pregnancy and underwent weekly fetal echocardiography from 18th to 26th weeks of gestational age. Infants' ECG and/or ECG-Holter were performed at 1, 3, 6 and 12 months. ECG of 200 consecutive neonates were used as a healthy control group. RESULTS: One of 61 fetuses of anti-Ro-positive mothers developed CHB (20th week); another anti-Ro-positive baby developed second degree atrioventricular (AV) block (30th week). The prevalence of transient first degree AV block detected post-natally was significantly higher in the anti-Ro-positive group, in comparison with healthy controls (P = 0.002). No differences in corrected QT (QTc) interval prolongation prevalence (>/=440 ms) was observed between the anti-Ro-positive and -negative groups, but both were significantly higher than that of the control population (P < 0.001). ECG-Holter showed QTc prolongation in 59% of infants of anti-Ro-positive and in 60% of infants of anti-Ro-negative mothers. Holter QTc was >/=470 ms in four infants of anti-Ro-positive group and two of anti-Ro-negative group. Known acquired causes of QTc prolongation were excluded. CONCLUSIONS: This prospective study confirms the low occurrence of CHB in newborns from anti-Ro-positive mothers. ECG abnormalities (first degree AV block and QTc interval prolongation) are frequent in infants of mothers with autoimmune diseases, independently of maternal disease, autoantibody profile and treatment during pregnancy.     

Blood microRNA changes in depressed patients during antidepressant treatment

MicroRNAs (miRNAs) are potent modulators of protein expression that play key roles in brain pathways regulating neurogenesis and synaptic plasticity. These small RNAs may be critical for the pathophysiology of mental disorders and may influence the effectiveness of psychotropic drugs. To investigate the possible involvement of miRNAs in the mechanism of action of antidepressants (AD), we conducted a whole-miRNome quantitative analysis with qRT-PCR of the changes in the blood of 10 depressed subjects after 12 weeks of treatment with escitalopram. Thirty miRNAs were differentially expressed after the AD treatment: 28 miRNAs were up-regulated, and 2 miRNAs were strongly down-regulated. miRNA target gene prediction and functional annotation analysis showed that there was a significant enrichment in several pathways associated with neuronal brain function (such as neuroactive ligand–receptor interaction, axon guidance, long-term potentiation and depression), supporting the hypothesis that the differentially regulated miRNAs may be involved in the AD mechanism.     

The syndrome of partial trisomy 14q

The case of a 4-month-old male with a de novo partial trisomy for chromosome 14 involving the p13q24 portion is reported. He presented with growth and psychomotor retardation, peculiar facies due to nose-mouth anomalies, monolateral microphtalmia, high arched palate, and anomalies of hands and feet. These symptoms are found also in the other 8 cases of partial trisomy 14 reported in the literature. This confirms a characteristic chromosomal syndrome although the breaking points on the extra chromosome 14 are not the same in the 9 cases. The clinical picture of our case calls for careful investigations of the chronology of bone age and of the immunologic situation in further cases of total and partial trisomy 14.     

Intratumoral delivery of mitoxantrone in association with 90-Y radioimmunotherapy (RIT) in recurrent glioblastoma

Summary Twenty-six recurrent Glioblastoma (rGBM) patients sequentially treated at the National Neurological Institute ‘C Besta’ were enrolled for a second surgery in order to remove recurrent tumor and to place an Ommaya reservoire to allow local delivery of chemotherapy and local pre-targeted radio-immunotherapy (RIT). All patients had partial tumor resection and 75% of them had a residual tumor mass after exeresis larger than 2 cm. After surgery all patients were managed with a second line systemic chemotherapy (PCV). Moreover the protocol scheduled two cycles of local RIT (90 Yttrium 5– 25 mCi per cycle) with a 10 week interval. Locoregional mitoxantrone chemotherapy was locally delivered as a single dose of 4 mg every 20 days. Responses to treatment were assessed by monthly neurological examination and by MRI or contrast-enhanced CT scan performed every 2 months.For the whole group of patients the PFS after second surgery at 6 and 12 months was 61% and 22%, respectively and survival after recurrence at 6, 12 and 18 months was 80%, 53% and 42%, respectively. Neither major side effects occurred systemically nor related on the place of local injections. The percentage of long-term survivors was very high: 42% of patients were still alive at 18 months. We stress the concept that the combined treatments could be more effective if delivered into a smaller residual tumor mass and probably in an adjuvant setting, before tumour recurrence.     

Arterial switch operation after left ventricular retraining in the adult

Retraining the morphological left ventricle in transposition of the great arteries has been successfully reported in infancy, while older age seems to be a contraindication. A 23-year-old woman with ?S,D,D? transposition of the great arteries and ventricular septal defect developed severe right systemic ventricular dysfunction 22 years after Mustard procedure and ventricular septal defect closure. Hemodynamic investigation revealed moderate pulmonary hypertension and preserved left ventricular function. A pulmonary artery band was applied to obtain a left-right ventricular pressure ratio of 0.91. Her postoperative course was characterized by biventricular failure, treated effectively with inotropic support. Six months later, she underwent a Mustard baffle takedown and arterial switch procedure. Her postoperative course was uneventful. She was discharged home on postoperative day 15. At 24-months follow-up, she is in excellent clinical condition; echocardiographic evaluation shows good left ventricular function (ejection fraction: 0.69) with left ventricular volume within normal limits (70 ml/m2). Our experience demonstrates that, despite adult age, a staged arterial switch operation can be performed successfully in selected patients when left ventricular function is preserved.