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Quantitative MR evaluation of intracranial epidermoid tumors by fast fluid-attenuated inversion recovery imaging and echo-planar diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Quantification of MR can provide objective, accurate criteria for evaluation of a given MR sequence. We quantitatively compared conventional MR sequences with fast fluid-attenuated inversion recovery (fast-FLAIR) and echo-planar diffusion-weighted (DW) MR imaging in the examination of intracranial epidermoid tumors. METHODS: Eight patients with surgically confirmed intracranial epidermoid tumors were examined with T1-weighted MR sequences, fast T2- and proton density-weighted dual-echo sequences, fast-FLAIR sequences, and DW echo-planar sequences. We measured the MR signal intensity and apparent diffusion coefficient (ADC) of epidermoid tumors, normal brain tissue, and CSF and calculated the tumor-to-brain and tumor-to-CSF contrast ratios and contrast-to-noise ratios (CNR). Results were compared among the five MR methods. RESULTS: On fast-FLAIR imaging, the mean signal intensity of epidermoid tumors was significantly higher than that of CSF but significantly lower than that of the brain; the contrast ratio and CNR of tumor-to-CSF were 4.71 and 9.17, respectively, significantly greater than the values with conventional MR imaging. On echo-planar DW imaging, epidermoid tumors showed a remarkably hyperintense signal relative to those of the brain and CSF; the mean contrast ratio and CNR of tumor-to-CSF were 13.25 and 19.34, respectively, significantly greater than those on fast-FLAIR or conventional MR imaging. The mean ADC of epidermoid tumors was 1.197 x 10(-3) mm(2)/s, significantly lower than that of CSF but higher than that of brain tissues. CONCLUSION: Fast-FLAIR imaging is superior to conventional MR imaging in depicting intracranial epidermoid tumors. Echo-planar DW imaging provides the best lesion conspicuity among the five MR methods. The hyperintensity of epidermoid tumors on echo-planar DW imaging is not caused by the diffusion restriction but by the T2 shine-through effect.

Aged↗

Dynamic contrast-enhanced MR imaging of perianal fistulas.

OBJECTIVE: The objective of this study was to prospectively compare dynamic contrast-enhanced MR imaging with MR sequences previously described for assessing perianal fistulas in order to determine the best MR protocol for their evaluation. SUBJECTS AND METHODS: MR examinations of 42 consecutive patients with clinically suspected perianal fistulas were independently evaluated by two experienced observers blinded to the findings of digital rectal examination. The observers' evaluations occurred before definitive surgical exploration. All patients had body-coil MR imaging examinations, including the following sequences that were ranked for anatomic and pathologic information: spin-echo T1-weighted, short inversion time inversion recovery, and dynamic contrast-enhanced MR imaging in the coronal plane; and spin-echo T2-weighted imaging in the axial plane. Surgical findings were accepted as the gold standard and were recorded independently by the surgeon, who was unaware of the findings of the MR assessment. MR findings were subsequently correlated with digital rectal examination before surgery and with clinical follow-up. RESULTS: MR imaging correctly allowed our blinded observers to predict the surgical anatomy of perianal disease in 37 of the 42 patients (accuracy, 88%). For detection of the presence and site of an enteric fistulous entry, MR imaging had a sensitivity of 97%, a specificity of 67%, a positive predictive value of 88%, and a negative predictive value of 89%. On MR imaging examination, eight patients had no fistula, 12 had simple intersphincteric fistulas, and 22 had complex fistulas. MR imaging revealed all 14 perianal abscesses and fluid collections found at surgery. Digital rectal examination before surgery failed to reveal abscesses or important secondary tracks in eight of the 22 complex fistulas. For anatomic and pathologic depiction of fistulas, dynamic contrast-enhanced MR imaging ranked as the best sequence for 22 of 34 fistulas. The short inversion time inversion recovery sequence, which was unable to distinguish small abscesses from perianal inflammation and showed spurious high signal in old fibrotic tracks, led our observers to misdiagnose five cases. In four patients for which initial surgery did not confirm enteric entry sites that our observers had predicted by MR imaging, follow-up has confirmed the observers' diagnoses. The observers' evaluations of the MR examinations agreed in 37 (88%) of the 42 cases. CONCLUSION: MR imaging is more accurate than digital rectal examination before surgery in detecting complex features of perianal fistulas. MR imaging is noninvasive, is highly accurate, and has low interobserver variability. With MR imaging, observers may better predict outcome than with initial surgical exploration. MR assessment that includes dynamic contrast-enhanced MR imaging and axial T2-weighted sequences (examination time, 20 min) provides the anatomic and pathologic information required to guide surgical management.

Adult↗

Landscapes: complex optimization problems and biopolymer structures.

The evolution of RNA molecules in replication assays, viroids and RNA viruses can be viewed as an adaptation process on a 'fitness' landscape. The dynamics of evolution is hence tightly linked to the structure of the underlying landscape. Global features of landscapes can be described by statistical measures like number of optima, lengths of walks and correlation functions. The evolution of a quasispecies on such landscapes exhibits three dynamical regimes depending on the replication fidelity: Above the "localization threshold" the population is centered around a (local) optimum. Between localization and "dispersion threshold" the population is still centered around a consensus sequence, which, however, changes in time. For very large mutation rates the population spreads in sequence space like a gas. The critical mutation rates separating the three domains depend strongly on characteristics properties of the fitness landscapes. Statistical characteristics of RNA landscapes are accessible by mathematical analysis and computer calculations on the level of secondary structures: these RNA landscapes belong to the same class as well known optimization problems and simple spin glass models. The notion of a landscape is extended to combinatory maps, thereby allowing for a direct statistical investigation of the sequence structure relationships of RNA at the level of secondary structures. Frequencies of structures are highly non-uniform: we find relatively few common and many rare ones, as expressed by a generalized form of Zipf's law. Using an algorithm for inverse folding we show that sequences sharing the same structure are distributed randomly over sequence space. Together with calculations of structure correlations and a survey of neutral mutations this provides convincing evidence that RNA landscapes are as simple as they could possibly be for evolutionary adaptation: Any desired secondary structure can be found close to an arbitrary initial sequence and at the same time almost all bases can be substituted sequentially without ever changing the shape of the molecule. Consequences of these results for evolutionary optimization, the early stages of life, and molecular biotechnology are discussed.

Adaptation, Biological↗

Imaging of bone marrow disease in the spine.

Bone marrow imaging has been greatly advanced with magnetic resonance (MR) imaging. Bone marrow contains fat and nonfat cells, which makes imaging with MR imaging the modality of choice, particularly within the spine. Any alteration within the marrow makeup is usually well seen with different MR imaging sequences. Conventional spin-echo sequences are helpful because of their great signal-to-noise ratio, and anatomic detail. Other, newer sequences--such as short T1 inversion recovery (STIR), diffusion weighted, fat suppression techniques; as well as in- and opposed-phase images--may also help to increase detection of or characterize certain diseases of the bone marrow within the spine. This article deals with the different imaging sequences available to radiologists when imaging the spinal bone marrow.

Bone Marrow Diseases↗

Manganese dipyridoxyl diphosphate. Effect of dose, time, and pulse sequence on hepatic enhancement in rats.

We used an animal model to investigate the hepatic enhancement characteristics of manganese dipyridoxyl diphosphate (MnDPDP) related to time, dose, and pulse sequence. The contrast doses selected were in the human tolerance range. Using an SE 300/15 pulse sequence, maximum mean hepatic enhancement of 45% (8 mumols/kg) and 58% (12 mumols/kg) over baseline was seen during a plateau maintained between 5 and 50 minutes postinjection in the 8 mumols/kg group, and between 10 and 90 minutes in the 12 mumols/kg group. This plateau was followed by a very gradual decline in hepatic enhancement. Using either 4 or 8 mumols/kg, there was a significant increase in postcontrast hepatic intensity on all relatively T1-weighted pulse sequences (spin echo [SE] 300/15, inversion recovery [IR] 1400/20/400, gradient echo [GE] 47/13/80 degrees, and GE 60/20/30 degrees) except GE 47/13/80 degrees at 4 mumols/kg. At 8 mumols/kg there was superior enhancement, with IR 1400/20/400 and SE 300/15, but at 4 mumols/kg there was no consistently superior sequence. None of the relatively T2-weighted pulse sequences (SE 2000/50, SE 2000/100, or GE 100/30/20 degrees) demonstrated a significant change in hepatic intensity using either dose of contrast. The data suggest that the best combination of dose, pulse sequence, and time for hepatic imaging with MnDPDP is 8 mumols/kg using heavily T1-weighted sequences 5 to 60 minutes following contrast administration.

Animals↗

Liver MR imaging: comparison of respiratory triggered fast spin echo with T2-weighted spin-echo and inversion recovery.

BACKGROUND: The purpose of this study was to compare a fast spin-echo sequence combined with a respiratory triggering device (R. trig. FSE) with conventional T2-weighted spin-echo (CSE) and inversion recovery (STIR) sequences for the detection of focal hepatic lesions. METHODS: We performed a prospective study of 33 consecutive patients with known or suspected hepatic tumors. All patients underwent R. trig. FSE, CSE, and STIR imaging at 1.5 T. Acquisition times were 10.7 min for the CSE sequence and ranged from 12 to 15 min for STIR and from 5 to 7 min for R. trig FSE. For each sequence, liver-spleen contrast-to-noise ratio (CNR) and liver-lesion CNR were determined quantitatively. Image artifact and sharpness were graded by using a four-point scale on each sequence by two independent readers. Both readers also independently identified hepatic lesions (up to a maximum of eight per patient). For patients with focal lesions, the total number of lesions detected (on each sequence) and the minimum size of detected lesions were also determined by each reader. RESULTS: No significant difference was detected between R. trig. FSE and CSE or STIR in either liver-spleen CNR or liver-lesion CNR. R. trig. FSE images were equivalent to CSE and superior to STIR in sharpness (p < 0.01) and presence of artifact (p < 0.01). R. trig. FSE detected a higher number of lesions (reader 1: n = 92, reader 2: n = 86) than CSE (reader 1: n = 70, reader 2: n = 69) and a significantly higher number than STIR (reader 1: n = 71, reader 2: n = 76). Lesion structure was significantly better defined with R. trig. FSE than with STIR (p < 0.01) and CSE (p < 0.05). CONCLUSIONS: Compared with CSE and STIR, R. trig. FSE produces hepatic images of comparable resolution and detects an increased number of focal hepatic lesions in a shorter period of time.

Adolescent↗

MR cisternography: a new method for the diagnosis of CSF fistulae.

The aim of this study was to compare a new MRI method for detecting the existence of cerebrospinal fluid (CSF) fistulae, i. e. MR cisternography, with CT cisternography. In a prospective study, 30 patients with post-traumatic CSF fistulae were examined. The MR examinations were performed with a 1.0-T whole-body MR system, using two T2(*)-weighted sequences, a 3D PSIF (time-inversed fast imaging with steady-state precession, FISP) and a 3D constructive interference steady-state (CISS) sequence. The results of MRI and CT cisternography were compared with the surgical findings. The sensitivity in detecting CSF fistulae with MR cisternography (PSIF: 89.9 %; CISS: 93.6 %) was higher than with CT cisternography (72.3 %). The sensitivity of CT cisternography at detecting CSF fistulae in patients with a size of dural lesion less than 2 mm or in patients with multiple dural lesions is significantly lower compared with the MR method. Although the localization of CSF fistulae always proved possible with MR cisternography, this could only be accomplished wih CT in 70 % of cases. The MR cisternography technique is a new examination method with a higher sensitivity for the detection of CSF fistulae than CT cisternography. The CISS technique is superior compared with PSIF and should be used in patients with high-flow CSF fistulas.

Adolescent↗

Liver imaging at 1.5 tesla: pulse sequence optimization based on improved measurement of tissue relaxation times.

In order to predict the most sensitive MR imaging sequence for detecting liver metastases at 1.5 T, in vivo measurements of T1 and T2 relaxation times and proton density were obtained using multipoint techniques. Based on these measurements, two-dimensional contrast contour plots were constructed demonstrating signal intensity contrast between hepatic lesions and surrounding liver parenchyma for different pulse sequences and pulse timing parameters. The data predict that inversion recovery spin echo (IRSE) imaging should yield the greatest contrast between liver metastases and liver parenchyma at 1.5 T, followed by short tau inversion recovery (STIR) and spin-echo (SE) pulse sequences. T2-weighted SE images provided greater liver/lesion contrast than T1-weighted SE pulse sequences. Calculated T1, T2, and proton density values of the spleen were similar to those of hepatic metastatic lesions, indicating that the signal intensity of the spleen may be used as an internal standard to predict the signal intensity of hepatic metastases on T1- and T2-weighted images at 1.5 T.

Adult↗

Identification of an alkaline ceramidase gene from Dermatophilus congolensis.

A random amplified polymorphic DNA (RAPD) procedure was used to identify a specific 0.6 kb DNA fragment unique to Dermatophilus congolensis. This 0.6 kb fragment was evaluated as a specific DNA probe and used to design oligonucleotide primers for polymerase chain reaction (PCR) amplification. The nucleotide sequences adjacent to this DNA fragment were determined by inverse PCR allowing the identification of a 4.1 kb sequence. Analysis of this revealed a complete open reading frame (ORF) with a high similarity to an alkaline ceramidase from Pseudomonas aeruginosa. The molecular weight of the enzyme derived from the predicted amino acid sequence is 74,662 Da, its pI is 9.81. The predicted N-terminal sequence of the enzyme contains a signal sequence indicating that the enzyme is exported by the bacterium. Since ceramides have important protective and cell regulatory roles in the epidermis we suggest that this ceramidase may have a role in the pathogenesis of dermatophilosis. It is the first completely sequenced gene described for D. congolensis.

Actinobacteria↗

Cloning and characterization of the mating type (MAT) locus from Ascochyta rabiei (teleomorph: Didymella rabiei) and a MAT phylogeny of legume-associated Ascochyta spp.

Degenerate primers designed to correspond to conserved regions of the high mobility group (HMG) protein encoded by the MAT1-2 gene of Cochliobolus heterostrophus, Cochliobolus sativus, and Alternaria alternata were used to amplify the portion of the sequence corresponding to the HMG box motif from Ascochyta rabiei (teleomorph: Didymella rabiei). A combination of TAIL and inverse PCR extended the MAT1-2 sequence in both directions, then primers designed to MAT1-2 flanking DNA were used to amplify the entire MAT1-1 idiomorph. MAT1-1 and MAT1-2 idiomorphs were 2294 and 2693 bp in length, respectively, and each contained a single putative open reading frame (ORF) and intron similar to MAT loci of other loculoascomycete fungi. MAT genes were expressed at high levels in rich medium. MAT-specific PCR primers were designed for use in a multiplex PCR assay and MAT-specific PCR amplicons correlated perfectly to mating phenotype of 35 ascospore progeny from a cross of MAT1-1 by MAT1-2 isolates and to the mating phenotype of field-collected isolates from diverse geographic locations. MAT-specific PCR was used to rapidly determine the mating type of isolates of A. rabiei sampled from chickpea fields in the US Pacific Northwest. Mating type ratios were not significantly different from 1:1 among isolates sampled from two commercial chickpea fields consistent with the hypothesis that these A. rabiei populations were randomly mating. The mating type ratio among isolates sampled from an experimental chickpea field where asexual reproduction was enforced differed significantly from 1:1. A phylogeny estimated among legume-associated Ascochyta spp. and related loculoascocmycete fungi using sequence data from the nuclear ribosomal internal transcribed spacer (ITS) demonstrated the monophyly of Ascochyta/Didymella spp. associated with legumes but was insufficiently variable to differentiate isolates associated with different legume hosts. In contrast, sequences of the HMG region of MAT1-2 were substantially more variable, revealing seven well-supported clades that correlated to host of isolation. A. rabiei on chickpea is phylogenetically distant from other legume-associated Ascochyta spp. and the specific status of A. rabiei, A. lentis, A. pisi, and A. fabae was confirmed by the HMG phylogeny

Amino Acid Sequence↗

Correlations between proton nuclear magnetic resonance imaging and retrospective histochemical images in experimental cerebral infarction.

Evaluation of ischemic brain injury in experimental cerebral infarction in gerbils and rats was performed by means of both proton nuclear magnetic resonance imaging ([1H]NMR-CT) and various histochemical analyses. In vivo nuclear magnetic resonance (NMR) imaging was carried out employing saturation recovery, inversion recovery, and spin echo pulse sequences. Spatial resolution of the images was excellent. The ischemic lesions were detected with a remarkable contrast in inversion recovery and spin echo images within a few hours after insult. Those changes in NMR images consistently corresponded with the various retrospective histochemical observations, especially with methods related to brain edema (K+ staining) rather than structural (enzymatic) studies. Calculated T1 and T2 relaxation times indicated the evolution of the edema state in the brain in situ. They correlated excellently with the retrospective water content measurement. As a result, detailed characterization of the edema state induced by cerebral ischemia was possible in vivo using [1H]NMR imaging.

Adenosine Triphosphatases↗

Cardiac gated breath-hold black blood MRI of the coronary artery wall: an in vivo and ex vivo comparison.

BACKGROUND: High resolution magnetic resonance (MR) imaging of the coronary artery wall in vivo has been limited by the cardiac and respiratory motion, flow artifacts as well as the relatively small size of the coronary arteries. We sought to validate in vivo black blood MR imaging of the coronary artery wall using a double inversion recovery fast spin echo MR imaging sequence with limited breath-holding and cardiac gating for suppression of motion artifacts by comparison with ex vivo MR imaging. METHODS: Yorkshire albino swine (n = 6) were used in this study and coronary lesions were induced with balloon angioplasty. Four weeks after balloon injury of the coronary arteries MR imaging of the coronary artery lesions was performed. High resolution in vivo and ex vivo images of the coronary artery wall and lesions were obtained using a double inversion recovery fast spin echo sequence in a 1.5 T MR system. There was a statistically significant agreement (p < 0.0001) between measurements of vessel wall area (r = 0.87, slope = 0.87) and maximal wall thickness (r = 0.84, slope = 0.88) from in vivo and ex vivo MR images of the coronary arteries. The mean differences between in vivo and ex vivo measurements were 0.56 +/- 1.98 mm2 for vessel wall area and 0.02 +/- 0.36 mm for maximal wall thickness. CONCLUSIONS: Using breathholding and cardiac gating, it is possible to perform high resolution MR imaging of the coronary artery wall in vivo with good suppression of motion artifacts with a double inversion recovery fast spin echo black blood imaging sequence.

Animals↗

Variable deletion and duplication at recombination junction ends: implication for staggered double-strand cleavage in class-switch recombination.

Immunoglobulin class-switch recombination (CSR) gives rise to looped-out circular DNA of a cleaved S segment, which is lost eventually after cell divisions. To understand the molecular mechanism of S region cleavage during CSR, we constructed artificial CSR substrates in which inversion-type CSR takes place to retain the cleaved S segment. Sequencing analyses of recombinant clones of these substrates revealed that varying degrees of deletions and duplications exist at CSR breakpoints, suggesting the involvement of staggered cleavage of the S region in CSR. In addition, mutations frequently found near junctions showed a similar profile of base replacement to Ig somatic hypermutation. These findings suggest that single-strand tails of staggered cleavage may be repaired by error-prone DNA synthesis.

Animals↗

Selective saturation and inversion of multiple resonances in high-resolution solid-state 13C experiments using slow spinning CP/MAS and tailored DANTE pulse sequences.

Taking advantage of the long 13C T1 values generally encountered in solids, selective saturation and inversion of more than one resonance in 13C CP/MAS experiments can be achieved by sequentially applying several DANTE pulse sequences centered at different transmitter frequency offsets. A new selective saturation pulse sequence is introduced composed of a series of 90 degrees DANTE sequences separated by interrupted decoupling periods during which the selected resonance is destroyed. Applications of this method, including the simplification of the measurement of the principal values of the 13C chemical shift tensor under slow MAS conditions, are described. The determination of the aromaticity of coal using a relatively slow MAS rate is also described.

Anisoles↗

Characterisation and interpopulation variability of a complex HpaI satellite DNA of Drosophila seriema (repleta group).

A HpaI satellite DNA has been isolated and characterised from the genome of Drosophila seriema, a cactus-breeding species endemic to the rock fields of the Espinhaço Range in Brazil. The monomer sequences are slightly A + T rich (66%) and there is a significant variation of repetition length (343-391 bp). The length variability is mainly due to a 22 bp indel in some repeats and the presence of a highly variable region characterised by several DNA rearrangements, including indels, inversions and duplications of small sequence segments. The retarded mobility of monomers observed after gel electrophoresis suggests DNA curvature. Thirty satDNA repeats were analysed in samples from five populations which cover D. seriema geographical distribution. Previous studies showed that these populations present low levels of chromosomal divergence in contrast to high levels of mtDNA divergence. The variability among the 30 repeats is pretty low, on average 2%. The results showed that the satDNA sequences are rather homogeneous on both intra and interpopulational levels, presenting no specific feature(s) that could discriminate a particular population or groups of geographically close populations. Possible factors responsible for such homogeneity are discussed.

Animals↗

Multiple sequence information for threading algorithms.

Threading algorithms attempt to solve the inverse protein folding problem: given a group of structures and a sequence, identify the structure that is most compatible with this sequence. A recent study of this class of algorithms by S. J. Wodak and colleagues suggests that while threading algorithms are capable of recognizing many folding motifs, their performance in truly blind predictions is disappointing, and the underlying alignments upon which the selections are based are frequently errant. To help overcome this problem we have developed a Test of Optimal Mutagenesis algorithm (TOM) that exploits information inherent in the variation between several homologues in a multiple sequence alignment. This information is used to help select the correct structural motif for the sequence from a database of known structures. A total of 305 high-resolution structures were selected to represent the set of known folds; 56 proteins were chosen that had at least one close structural match in this set. To test TOM, we attempted to determine which of the 305 folds was a match to each of the 56 protein sequences. TOM correctly predicts a close structural match for 45% of these proteins. THREADER, an algorithm chosen as a literature standard, correctly matched 20% of the test set. By comparing the performance of TOM, THREADER, and TOM NOVAR (a version of TOM without variability information), we conclude that the tendency of an amino acid to be buried or exposed is the dominant determinant of the success of threading algorithms. In addition, the structural alignments produced by TOM suggest that the exact alignment of just 30 to 50% of the residues in a sequence with the correct fold is necessary to select it as the highest scoring match in a set of folds.

Algorithms↗

A method to identify protein sequences that fold into a known three-dimensional structure.

The inverse protein folding problem, the problem of finding which amino acid sequences fold into a known three-dimensional (3D) structure, can be effectively attacked by finding sequences that are most compatible with the environments of the residues in the 3D structure. The environments are described by: (i) the area of the residue buried in the protein and inaccessible to solvent; (ii) the fraction of side-chain area that is covered by polar atoms (O and N); and (iii) the local secondary structure. Examples of this 3D profile method are presented for four families of proteins: the globins, cyclic AMP (adenosine 3',5'-monophosphate) receptor-like proteins, the periplasmic binding proteins, and the actins. This method is able to detect the structural similarity of the actins and 70- kilodalton heat shock proteins, even though these protein families share no detectable sequence similarity.

Actins↗

Mechanism of antigenic variation in Mycoplasma pulmonis: interwoven, site-specific DNA inversions.

The chromosome of the murine pathogen Mycoplasma pulmonis undergoes rearrangements at a high frequency. We show that some of these rearrangements regulate the phase-variable expression of a cluster of genes (the vsa locus) that encode the variable V-1 surface antigens. Only one vsa gene is associated with an expression site; the other vsa genes are transcriptionally silent. The silent genes lack the 5' end region (promoter and ribosome-binding site) that is present in the expressed gene, and DNA rearrangements regulate gene expression by reassorting the 5' end region from an expressed gene with the 3' end region from a previously silent gene. All vsa rearrangements identified so far are site-specific DNA inversions that occur between copies of a specific 34 bp sequence that is conserved in each vsa gene. Interestingly, DNA inversions within the vsa locus apparently occur in concert with inversion of the hsd1 element, which regulates restriction and modification activity in M. pulmonis.

Amino Acid Sequence↗