White matter abnormalities are related to microstructural changes in preterm neonates at term-equivalent age: a diffusion tensor imaging and probabilistic tractography study.

BACKGROUND AND PURPOSE: Preterm infants have a high risk of brain injury and neurodevelopmental impairment, often associated with WMA on conventional MR imaging. DTI can provide insight into white matter microstructure. The aim of this study was to investigate the association between WMA on conventional MR imaging and DTI parameters in specific fibers in preterm neonates at term-equivalent age. MATERIALS AND METHODS: Seventy preterm neonates (39 boys and 31 girls) were included in the study. WMA were classified as no, mild, moderate, or severe. Probabilistic tractography provided tract volumes, FA, MD, λ(//), and λ(⊥) in the CST, SLF, TRs, and corpus callosum. Data were compared by using MANOVA, and adjustment for multiple comparisons was performed. RESULTS: Important associations were found between WMA and microstructural changes. Compared with neonates with no WMA (n = 41), those with mild WMA (n = 27) had significantly increased λ(⊥) and MD in the left ATR, the left sensory STR, the bilateral motor STR, and for λ(⊥) also in the right CST; FA decreased significantly in the left sensory STR. Diminished tract volumes and altered diffusion indices were also observed in the 2 neonates with moderate WMA. CONCLUSIONS: Altered DTI indices in specific tracts, with λ(⊥) as most prominent, are associated with mild WMA in preterm neonates at term-equivalent age.

What is the optimal b value in diffusion-weighted MR imaging to depict prostate cancer at 3T?

OBJECTIVE: To determine an optimal b value to visualise prostate cancer using diffusion-weighted magnetic resonance imaging at 3 T. METHODS: Forty one patients with biopsy proven prostate cancer underwent 3 T diffusion-weighted MRI performed with 5 b values (0, 1,000, 1,500, 2,000, 2,500 s/mm(2)) using a 16-channel coil. Best lesion visibility, the central gland-lesion (CG-L) and the peripheral zone-lesion (PZ-L) contrast-to-noise ratio (CNR) were compared between different b value images, apparent diffusion coefficient (ADC) were measured. In a subset of 29 patients a high resolution b1,500 s/mm(2)diffusion-weighted sequence was additionally assessed. RESULTS: The b = 1,500 s/mm(2) and b = 2,000 s/mm(2) images provided the best lesion visibility respectively in 27/41 and in 10/41 patients. The highest CG-L and PZ-L CNR were obtained with b = 1,500 s/mm(2) (P < 0.0001). The mean ADC value calculated from 0 to 1,500 s/mm(2) b values in cancer lesions (ADC = 736 ± 173 10(-6) mm(2)/s) was statistically significantly lower than in the peripheral zone (ADC = 1,338 ± 256 10(-6) mm(2)/s, P < 0.0001) and in the central gland (ADC = 1,270 ± 239 10(-6) mm(2)/s, P < 0.0001). The high resolution diffusion sequence was judged of better lesion visibility than (17/29) or equivalent to (6/29) the best images from the 5b sequence. CONCLUSION: At 3 T, prostate cancer lesions are best depicted with b = 1,500 s/mm(2) and b = 2,000 s/mm(2) images, b = 1,500 s/mm(2) high-resolution diffusion images improve the image quality and contrast. KEY POINTS: • Multiple b ≥ 1,000 s/mm ( 2 ) 3 T-DW Magnetic Resonance Imaging provides excellent prostate cancer depiction. • Prostate DWI and ADC maps are attainable at 3 T without endorectal coil. • Prostate cancer depiction is improved on high resolution b 1,500 s/mm ( 2 ) 3 T-DWI.

Gender differences in language and motor-related fibers in a population of healthy preterm neonates at term-equivalent age: a diffusion tensor and probabilistic tractography study.

BACKGROUND AND PURPOSE: Sex differences in white matter structure are controversial. In this MR imaging study, we aimed to investigate possible sex differences in language and motor-related tracts in healthy preterm neonates by using DTI and probabilistic tractography. MATERIALS AND METHODS: Thirty-eight preterm neonates (19 boys and 19 girls, age-matched), healthy at term-equivalent age and at 12 months were included. TBV was measured individually. Probabilistic tractography provided tract volumes, relative tract volumes (volume normalized to TBV), FA, MD, and λ(⊥) in the SLF, in the TRs, and in the CSTs. Data were compared by using independent t tests, and Bonferroni corrections were performed to adjust for multiple comparisons. RESULTS: We showed that healthy preterm boys had larger TBV than girls. However, girls had statistically significantly larger relative tract volumes than boys bilaterally in the parieto-temporal SLF, and in the left CST. Moreover, in the left parieto-temporal SLF, a trend toward lower MD and λ(⊥) was observed in females. CONCLUSIONS: Structural sex differences were found in preterm neonates at term-equivalent age in both sides of the parieto-temporal SLF and in the left CST. Further studies are necessary to investigate whether these structural differences are related to later sex differences in language skills and handedness or to the effect of prematurity.

Fat attenuation using a dual steady-state balanced-SSFP sequence with periodically variable flip angles.

A refocused-SSFP sequence based on balanced-FFE (TrueFisp, Fiesta) that attenuates fat signal is presented. The sequence uses periodically variable flip angles and produces a dual steady state of the signal, which is obtained after a dual transient phase if an appropriate preparation is used. The off-resonance profile of the steady-state signal exhibits large stopbands that can be employed for fat suppression. Numerical simulations were performed to investigate the signal behavior and the off-resonance properties of the sequence. Experimental results obtained with a Philips Gyroscan Intera 1.5T MR scanner demonstrated fat attenuation in phantoms and abdominal images in volunteers.

Site-directed mutagenesis of mouse dihydrofolate reductase. Mutants with increased resistance to methotrexate and trimethoprim.

Site-directed mutagenesis was used to generate mutants of recombinant mouse dihydrofolate reductase to test the role of some amino acids in the binding of two inhibitors, methotrexate and trimethoprim. Eleven mutations changing eight amino acids at positions all involved in hydrogen bonding or hydrophobic interactions with dihydrofolate or one of the two inhibitors were tested. Nine mutants were obtained by site-directed mutagenesis and two were spontaneous mutants previously obtained by in vivo selection (Grange, T., Kunst, F., Thillet, J., Ribadeau-Dumas, B., Mousseron, S., Hung, A., Jami, J., and Pictet, R. (1984) Nucleic Acids Res. 12, 3585-3601). The choice of the mutated positions was based on the knowledge of the active site of chicken dihydrofolate reductase established by x-ray crystallographic studies since the sequences of all known eucaryotic dihydrofolate reductases are greatly conserved. Enzymes were produced in great amounts and purified using a plasmid expressing the mouse cDNA into a dihydrofolate reductase-deficient Escherichia coli strain. The functional properties of recombinant mouse dihydrofolate reductase purified from bacterial extracts were identical to those of dihydrofolate reductase isolated from eucaryotic cells. The Km(NADPH) values for all the mutants except one (Leu-22----Arg) were only slightly modified, suggesting that the mutations had only minor effects on the ternary conformation of the enzyme. In contrast, all Km(H2folate) values were increased, since the mutations were located in the dihydrofolate binding site. The catalytic activity was also modified for five mutants with, respectively, a 6-, 10-, 36-, and 60-fold decrease of Vmax for Phe-31----Arg, Ile-7----Ser, Trp 24----Arg and Leu-22----Arg mutants and a 2-fold increase for Val-115----Pro. All the mutations affected the binding of methotrexate and six, the binding of trimethoprim: Ile-7----Ser, Leu-22----Arg, Trp-24----Arg, Phe-31----Arg, Gln-35----Pro and Phe-34----Leu. The relative variation of Ki for methotrexate and trimethoprim were not comparable from one mutant to the next, reflecting the different binding modes of the two inhibitors. The mutations which yielded the greatest increases in Ki are those which involved amino acids making hydrophobic contacts with the inhibitor.

Pancreatic expression of human insulin gene in transgenic mice.

We have investigated the possibility of obtaining integration and expression of a native human gene in transgenic mice. An 11-kilobase (kb) human chromosomal DNA fragment including the insulin gene (1430 base pairs) was microinjected into fertilized mouse eggs. This fragment was present in the genomic DNA of several developing animals. One transgenic mouse and its progeny were analyzed for expression of the foreign gene. Synthesis and release of human insulin was revealed by detection of the human C-peptide in the plasma and urine. Human insulin mRNA was found in pancreas but not in other tissues. These findings indicate that the 11-kb human DNA fragment carries the sequences necessary for tissue-specific expression of the insulin gene and the human regulatory sequences react to homologous signals in the mouse.

Electrophoretically distinct forms of uridine kinase in the rat. Tissue distribution and age-dependence.

By the use of polyacrylamide-gel electrophoresis, uridine kinase from foetal rat liver was separated into four types designated I, II, III and IV in decreasing order of mobility towards the anode. The most anodic (type I) was found only in rapidly growing tissues, such as foetal liver and brain, postnatal spleen and tumour cells. In adult tissues, types II, III and IV were found in the kidney, and types III and IV in the spleen and the liver, whereas type IV was the sole form of uridine kinase present in the brain.