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Contrast-enhanced cardiac magnetic resonance in a patient with familial isolated ventricular non-compaction.

Isolated ventricular non-compaction (IVNC) is an idiopathic form of cardiomyopathy. Recent clinical reports have suggested that this form of cardiomyopathy is more frequently associated with complications of congestive heart failure, thromboembolism and malignant ventricular arrhythmias. Contrast enhanced cardiac magnetic resonance imaging with its excellent spatial resolution, its large field of view and its ability to demonstrate thrombus and myocardial scar is an excellent modality to non-invasively assess patients with this form of cardiomyopathy. This paper presents a case of familial isolated ventricular non-compaction. We describe the echocardiographic, X-ray angiographic and cardiac MRI findings. Cine imaging using a steady-state free precession sequence (BFFE) was performed in axial and short axis planes. Left ventricular (LV) mass was estimated both with and without the incorporation of trabeculations from a contiguous stack of short axis images. Trabecular mass was expressed as a percentage of total left ventricular mass. We compared trabecular mass: total LV mass in 10 patients with dilated cardiomyopathy. The mean percentage trabecular mass: LV mass in dilated cardiomyopathy was 11.3% (range 1.5%-19%), and this differed significantly from the trabecular mass of the noncompaction patient (two-tailed Mann-Whitney test, p = 0.028). Trabecular mass of greater than 20% of total myocardial mass may be a useful index to suggest the diagnosis of IVNC. Gadolinium was administered (0.1 mmol/kg). Qualitative analysis of first pass perfusion suggested reduced trabecular perfusion. Early imaging with an inversion recovery sequence and a fixed long inversion time did not demonstrate LV thrombus. Late imaging with the same sequence (TI = 280-300 msec) did not demonstrate myocardial fibrosis.

Adult↗

Comparison of different pulse sequences for in vivo determination of T1 relaxation times in the human brain.

Quantitative in vivo determination of T1 relaxation times by magnetic resonance imaging (MRI) is hampered by several potential sources of error. This study focused on the influence of the radiofrequency pulse sequences applied with special attention to the significance of the repetition time (TR). T1 measurements were performed on the human brain using a whole body MR scanner operating at 1.5 tesla. Three different pulse sequences were compared including two 6-points inversion recovery (IR) sequences with TR = 2.0 s and 4.0, respectively, and a 12-points partial saturation inversion recovery (PSIR) sequence with TR varying between 0.24 and 8.0 s. The median T1 relaxation times obtained in cortical grey matter and cerebrospinal fluid were significantly shorter in the IR experiments at TR = 2 s than in those carried out at TR = 4 s. Concerning white matter the discrepancy was much less pronounced, but still statistically significant. Supplementary phantom measurements indicated that the higher T1 values are increasingly underestimated when TR is reduced to 2 s. The results suggest that the PSIR sequence or IR sequences with a TR greater than 2 X the T1 level of the tissue type investigated should be employed for accurate T1 determination by MRI in clinical work.

Brain↗

T1 relaxation time mapping of white matter tracts in multiple sclerosis defined by diffusion tensor imaging.

T(1) relaxation time (T(1)) is a quantitative magnetic resonance measure that enables a global evaluation of white matter disease in multiple sclerosis (MS). We aimed to investigate whether mapping of T(1) values in critical white matter tracts, defined by diffusion tensor (DT) imaging, could provide a stronger surrogate marker of disability. 25 patients with relapsing-remitting MS and 14 healthy controls were imaged with a dual-echo T(2)-weighted sequence. Whole brain T(1) maps were acquired using a multi-slice inversion recovery sequence and DT images generated from a spin-echo, echo-planar diffusion weighted sequence. Trajectories were defined to follow the course of white matter fibre tracts in the pyramidal pathways and corpus callosum. T(1) values were sampled along these trajectories. Total white matter T(1) was sampled by defining white matter masks on axial slices of the T(1) maps. Median T(1) in the pyramidal tracts, corpus callosum and total white matter of MS patients was significantly longer than in controls (p < 0.0001). Median pyramidal tract T(1) correlated significantly with the pyramidal Kurtzke Functional Systems Score (r = 0.64, p = 0.0007) and the Expanded Disability Status Scale (r = 0.55, p = 0.005). By contrast, no correlation with disability was observed for corpus callosum T(1) or total white matter T(1). Our findings show that quantifying pathology within the pyramidal tracts, by utilizing T(1), provides a strong correlate of disability compared with the overall white matter burden of disease. Pyramidal tract T(1) may also provide an objective, sensitive measure for monitoring the progression of motor deficits and disability.

Adult↗

MRI in multiple sclerosis of the spinal cord: evaluation of fast short-tan inversion-recovery and spin-echo sequences.

We compared the sensitivity of T2-weighted spin-echo (FSE) and fast short-tau inversion-recovery (fSTIR) sequences in detection of multiple sclerosis of the spinal cord in 100 consecutive patients with clinically confirmed multiple sclerosis (MS); 86 patients underwent also brain MRI. In all, 310 focal lesions were detected on fSTIR and 212 on T2-weighted FSE, spinal cord lesions were seen better on fSTIR images, with a higher contrast between the lesion and the normal spinal cord. In 24 patients in whom cord plaques were shown with both sequences, the cranial study was normal or inconclusive. Assessment of spinal plaques can be particularly important when MRI of the brain is inconclusive, and in there situations fSTIR can be helpful.

Adult↗

The myotonic dystrophy type 1 triplet repeat sequence induces gross deletions and inversions.

The capacity of (CTG.CAG)n and (GAA.TTC)n repeat tracts in plasmids to induce mutations in DNA flanking regions was evaluated in Escherichia coli. Long repeats of these sequences are involved in the etiology of myotonic dystrophy type 1 and Friedreich's ataxia, respectively. Long (CTG.CAG)n (where n = 98 and 175) caused the deletion of most, or all, of the repeats and the flanking GFP gene. Deletions of 0.6-1.8 kbp were found as well as inversions. Shorter repeat tracts (where n = 0 or 17) were essentially inert, as observed for the (GAA.TTC)176-containing plasmid. The orientation of the triplet repeat sequence (TRS) relative to the unidirectional origin of replication had a pronounced effect, signaling the participation of replication and/or repair systems. Also, when the TRS was transcribed, the level of deletions was greatly elevated. Under certain conditions, 30-50% of the products contained gross deletions. DNA sequence analyses of the breakpoint junctions in 47 deletions revealed the presence of 1-8-bp direct or inverted homologies in all cases. Also, the presence of non-B folded conformations (i.e. slipped structures, cruciforms, or triplexes) at or near the breakpoints was predicted in all cases. This genetic behavior, which was previously unrecognized for a TRS, may provide the basis for a new type of instability of the myotonic dystrophy protein kinase (DMPK) gene in patients with a full mutation.

Base Sequence↗

[In vitro study of morphology of the bladder wall using MR tomography at 1.0 Tesla: correlation with histology].

PURPOSE: Evaluation of the potential of various MR techniques to differentiate bladder wall layers verified by histological findings. MATERIAL AND METHOD: 6 bladder specimens of pigs were examined in vitro using T1-weighted spin-echo-sequences, T2-weighted Turbo-SE, fat suppressed T2-weighted SE, and inversion recovery sequences. The MR images were obtained before and after fixating the specimens in formalin. Measurements of the thickness of bladder wall layers were performed on both sets of MR images as well as on histological sections, RESULTS: T2-weighted SE images showed three layers of different signal intensities: one innermost band of very high signal, one inner band of low and one outer band of intermediate signal corresponding histologically tunica propria and two different muscle layers. Inversion recovery technique provided similar findings but were able to avoid chemical-shift artifacts. After 24 hours in formalin, the signal intensity relation of the two muscle layers was inverted. The thickness of total bladder wall was not reduced significantly. Concerning the thickness of urinary bladder wall, histological measurements and evaluation of MR images correlated well. CONCLUSION: MR imaging enables the differentiation of three bladder wall layers. Inversion recovery technique achieved the best image quality by avoiding chemical shift artifact.

Animals↗

Generation of adenovirus vectors devoid of all viral genes by recombination between inverted repeats.

Direct or inverse repeated sequences are important functional features of prokaryotic and eukaryotic genomes. Considering the unique mechanism, involving single-stranded genomic intermediates, by which adenovirus (Ad) replicates its genome, we investigated whether repetitive homologous sequences inserted into E1-deleted adenoviral vectors would affect replication of viral DNA. In these studies we found that inverted repeats (IRs) inserted into the E1 region could mediate predictable genomic rearrangements, resulting in vector genomes devoid of all viral genes. These genomes (termed DeltaAd.IR) contained only the transgene cassette flanked on both sides by precisely duplicated IRs, Ad packaging signals, and Ad inverted terminal repeat sequences. Generation of DeltaAd.IR genomes could also be achieved by coinfecting two viruses, each providing one inverse homology element. The formation of DeltaAd.IR genomes required Ad DNA replication and appeared to involve recombination between the homologous inverted sequences. The formation of DeltaAd. IR genomes did not depend on the sequence within or adjacent to the inverted repeat elements. The small DeltaAd.IR vector genomes were efficiently packaged into functional Ad particles. All functions for DeltaAd.IR replication and packaging were provided by the full-length genome amplified in the same cell. DeltaAd.IR vectors were produced at a yield of approximately 10(4) particles per cell, which could be separated from virions with full-length genomes based on their lighter buoyant density. DeltaAd.IR vectors infected cultured cells with the same efficiency as first-generation vectors; however, transgene expression was only transient due to the instability of deleted genomes within transduced cells. The finding that IRs present within Ad vector genomes can mediate precise genetic rearrangements has important implications for the development of new vectors for gene therapy approaches.

Adenoviridae↗

Construction of chromosomal rearrangements in Salmonella by transduction: inversions of non-permissive segments are not lethal.

Homologous sequences placed in inverse order at particular separated sites in the bacterial chromosome (termed "permissive") can recombine to form an inversion of the intervening chromosome segment. When the same repeated sequences flank other chromosome segments ("non-permissive"), recombination occurs but the expected inversion rearrangement is not found among the products. The failure to recover inversions of non-permissive chromosomal segments could be due to lethal effects of the final rearrangement. Alternatively, local chromosomal features might pose barriers to reciprocal exchanges between sequences at particular sites and could thereby prevent formation of inversions of the region between such sites. To distinguish between these two possibilities, we have constructed inversions of two non-permissive intervals by means of phage P22-mediated transduction crosses. These crosses generate inversions by simultaneous incorporation of two transduced fragments, each with a sequence that forms one join-point of the final inversion. We constructed inversions of the non-permissive intervals trp ('34) to his ('42) and his ('42) to cysA ('50). Strains with the constructed inversions are viable and grow normally. These results show that our previous failure to detect formation of these inversions by recombination between chromosomal sequences was not due to lethal effects of the final rearrangement. We infer that the "non-permissive" character of some chromosomal segments reflects the inability of the recombination system to perform the needed exchanges between inverse order sequences at particular sites. Apparently these mechanistic problems were circumvented by the transductional method used here to direct inversion formation.

Chromosome Inversion↗

Post-trial sleep sequences including transition sleep are involved in avoidance learning of adult rats.

High resolution computerized EEG analyses, and behavioral observations were used to identify slow wave sleep (SS), paradoxical sleep (PS) and transition sleep (TS) in adult male Wistar rats exposed to a session of two-way active avoidance training. Of the four sleep sequences that could be identified, two included TS (SS-->TS-->W and SS-->TS-->PS), while the other two did not (SS-->W and SS-->PS). Comparison of post-trial sleep variables between fast learning rats (FL, reaching criterion in the training session), slow learning rats (SL, reaching criterion in the retention session the following day), and non learning rats (NL, failing to reach criterion) indicated that the total amounts of SS, TS and PS of the SS-->TS-->PS sequence was markedly higher in FL rats than in SL rats. In addition, in comparison with the corresponding baseline period, the average duration and total amount of SS and TS episodes of the SS-->TS-->PS sequence increased in FL rats, while the number of SS-->TS-->W sequences decreased. On the other hand, the average duration of SS episodes increased in the SS-->TS-->W and SS-->W sequences of SL rats, and in the SS-->W and SS-->TS-->PS sequences of NL rats. Correlative analyses between number of avoidances and post-trial sleep variables demonstrated that avoidances were directly correlated with the duration of SS episodes of the SS-->TS-->PS sequence and with the duration of TS episodes of the SS-->TS-->W sequence, but inversely correlated with the number and amount of SS episodes of the SS-->W sequence and with the duration and amount of SS episodes of the SS-->PS sequence. On the whole, the data supported the view that TS-containing sleep sequences are involved in long-term storage of novel adaptive behavior, while sleep sequences lacking TS are involved in the maintenance of innate behavioral responses.

Animals↗

Exactly soluble hierarchical clustering model: inverse cascades, self-similarity, and scaling.

We show how clustering as a general hierarchical dynamical process proceeds via a sequence of inverse cascades to produce self-similar scaling, as an intermediate asymptotic, which then truncates at the largest spatial scales. We show how this model can provide a general explanation for the behavior of several models that has been described as "self-organized critical," including forest-fire, sandpile, and slider-block models.

Journal Article↗

Detailed comparative map of human chromosome 19q and related regions of the mouse genome.

One of the larger contiguous blocks of mouse-human genomic homology includes the proximal portion of mouse chromosome 7 and the long arm of human chromosome 19. Previous studies have demonstrated the close relationship between the two regions, but have also indicated significant rearrangements in the relative orders of homologous mouse and human genes. Here we present the genetic locations of the homologs of 42 human chromosome 19q markers in the mouse, with an emphasis on genes also included in the human chromosome 19 physical map. Our results demonstrate that despite an overall inversion of sequences relative to the centromere, apparent "transpositions" of three gene-rich segments, and a local inversion of markers mapping near the 19q telomere, gene content, order, and spacing are remarkably well conserved throughout the lengths of these related mouse and human regions. Although most human 19q markers have remained genetically linked in mouse, one small human segment forms a separate region of homology between human chromosome 19q and mouse chromosome 17. Three of the four rearrangements of mouse versus human 19q sequences involve segments that are located directly adjacent to each other in 19q13.3-q13.4, suggesting either the coincident occurrence of these events or their common association with unstable DNA sequences. These data permit an unusually in-depth examination of this large region of mouse-human genomic homology and provide an important new tool to aid in the mapping of genes and associated phenotypes in both species.

Animals↗

T1 measurements with clinical MR units.

To improve accuracy and feasibility of the proton spin-lattice relaxation time (T1) measurements in routine Magnetic Resonance Imaging (MRI), a phantom with polyvinyl alcohol gels and gadrinium diethylene triamine pentaacetic acid solutions was imaged with 1.5T clinical MR units and T1s were calculated by fitting several models to the observed signal intensities. When an inversion-recovery sequence was applied, we were able to measure T1 with a high degree of precision by taking into account the imperfection of the inversion pulse. With a Turbo-fast low angle shot sequence, we were able to obtain T1 in a short time, but low signal-to-noise ratio limited the precision. Signal intensity with SE sequence was susceptible to variation with the effective flip angle of 90 degrees RF pulse and not suited for T1 measurement.

Image Processing, Computer-Assisted↗

MR evaluation of vertebral metastases: T1-weighted, short-inversion-time inversion recovery, fast spin-echo, and inversion-recovery fast spin-echo sequences.

PURPOSE: To compare the detectability of vertebral metastatic disease on T1-weighted, short-inversion-time inversion recovery (STIR), fast spin-echo (FSE), fat-saturated FSE, and inversion recovery FSE (IRFSE) MR sequences using percent contrast and contrast-to-noise ratios. METHODS: Patients with proved metastatic disease underwent imaging on a 1.5-T MR system with sagittal T1-weighted (800/20/2 [repetition time/echo time/excitations]) (91 patients), STIR (1400/43/2; inversion time, 140) (91 patients), FSE (4000/180/2) (46 patients), fat-saturated FSE (4000/180/2) (16 patients), and IRFSE (29 patients) sequences. Percent contrast and contrast-to-noise ratio were calculated for the lesions. The number of metastatic lesions detected with each of the pulse sequences was also calculated. RESULTS: Mean percent contrast was, for T1-weighted sequence, -42.2 +/- 1%; STIR, 262 +/- 34%; FSE, 121 +/- 21%; fat-saturated FSE, 182 +/- 6%; and IRFSE, 272 +/- 47%. The mean contrast-to-noise ratio for T1-weighted was -4.63 +/- 1.7; STIR, 10.8 +/- .98; FSE, 4.16 +/- .76; fat-saturated FSE, 4.87 +/- .19; and IRFSE, 5.2 +/- .87. STIR and IRFSE showed the highest number of lesions, followed by T1-weighted, fat-saturated FSE, and FSE sequences. T1-weighted sequences showed 94%, FSE 55%, and fat-saturated FSE 78% of the lesions detected. Epidural metastatic lesions were better depicted on T1-weighted, FSE, and fat-saturated FSE sequences. CONCLUSION: STIR was superior to both T1-weighted and FSE (with and without fat saturation) for detection of metastatic lesions, in terms of both percent contrast and contrast-to-noise ratio and visibility. IRFSE was equal to STIR for the detection of metastasis by both subjective and objective criteria. T1-weighted, FSE, and fat-saturated FSE sequences were superior to STIR and IRFSE in the detection of epidural metastatic disease. IRFSE provided faster scanning time, which could be translated into greater resolution.

Adolescent↗

[Diagnosis of acute subarachnoid hemorrhage--MRI with 0.5 Tesla with FLAIR sequence].

PURPOSE: Evaluation of MR imaging in patients with acute subarachnoid hemorrhage (SAH) at 0.5 Tesla using the FLAIR (Fluid Attenuated Inversion Recovery) sequence. Additionally, the value of MR angiography (MRA) in the diagnosis of intracranial aneurysms was assessed. MATERIALS AND METHODS: 19 patients with suspected acute SAH were included in this study. MR imaging was performed using an axial FLAIR sequence and axial T1, T2 and PD weighted sequences. In 16 patients an additional MRA (3D-TOF) was performed. 10 patients without SAH were examined as a control group. At the end of the study the 29 MR examinations were randomised and the images were read by two experienced radiologists; subsequently a consensus interpretation was made. RESULTS: In 16 patients an acute SAH was verified with the FLAIR sequence, in 13 cases the origin of hemorrhage was found during surgery. In the consensus interpretation of the MR images all cases were diagnosed properly. 12 of the 16 MRA studies were of diagnostic quality, but only 6 cases were interpreted correctly. CONCLUSION: The FLAIR sequence at 0.5 Tesla proved effective in the diagnosis of acute SAH. MRA at 0.5 Tesla failed in the detection of intracranial aneurysms.

Acute Disease↗

Mobilisation of the streptococcal plasmid pMV158: interactions of MobM protein with its cognate oriT DNA region.

The streptococcal plasmid pMV158 encodes the relaxase protein, MobM, involved in its mobilisation. Purified MobM protein specifically cleaved supercoiled or single-stranded DNA containing the plasmid origin of transfer, oriT. Gel retardation and DNase I footprinting assays performed with DNA fragments containing the plasmid oriT provided evidence for specific binding of MobM by oriT DNA. Dissection of the MobM-binding sequence revealed that the oriT region protected by MobM spanned 28 nucleotides, and includes an inversely repeated sequence, termed IR2. MobM exhibits a high degree of similarity with the mob gene product of the Streptococcus ferus plasmid pVA380-1. Although the origins of transfer of pMV158 and pVA380-1 show 20% sequence divergence in a 24-bp sequence included in their oriT regions, the pMV158 MobM was able to cleave a supercoiled derivative of pVA380-1 in vitro.

Amino Acid Sequence↗

Ulnar collateral ligament in the growing elbow: MR imaging of normal development and throwing injuries.

PURPOSE: To study the magnetic resonance (MR) imaging appearance of the ulnar collateral ligament (UCL) and its insertion into the medial epicondyle. MATERIALS AND METHODS: Sixteen normal and 20 symptomatic elbows were examined with a 1.5-T unit. Normal elbows were imaged with axial T2*-weighted three-dimensional Fourier transform sequences. Symptomatic elbows were imaged with coronal T1-, T2-, and T2*-weighted and/or short-inversion-time inversion-recovery sequences. RESULTS: In normal immature elbows, the ulnar periosteum was seen as an extension of the UCL, and its enthesis had signal intensity characteristics that differed from those of the mature ligament. In symptomatic elbows imaged before epiphyseal fusion, segmentation and subchondral bone resorption of the ossification center were seen with or without a capsular tear. After epiphyseal fusion, a full-thickness or a partial UCL tear at the site of its insertion, with or without subcortical bone resorption, was seen. CONCLUSION: The MR imaging characteristics of the developing elbow differ from those of the mature elbow. MR imaging is useful in assessing UCL damage.

Adolescent↗

Inversion in the steady state: contrast optimization and reduced imaging time with fast three-dimensional inversion-recovery-prepared GRE pulse sequences.

PURPOSE: To evaluate the differences in contrast between 1-second delay and zero delay (for magnetization recovery) before the preparation radio-frequency pulse in three-dimensional, inversion-recovery (IR) fast gradient-echo (GRE) acquisitions. MATERIALS AND METHODS: Mathematical simulations and measurements of brain image contrast were performed with healthy volunteers and 10 patients. RESULTS: The zero-delay sequence generated T1-weighted contrast similar to that obtained with 1-second delay but was accompanied by a substantial reduction in imaging time. However, the zero delay prohibits full recovery of the longitudinal magnetization. Hence, the signal null characteristic of IR experiments is not easily observed, since it occurs (as a function of tissue T1) at very short inversion times (< 150 msec). CONCLUSION: T1-weighted contrast comparable with that of magnetization-prepared rapid GRE sequences with a 1-second delay and preparation time (TP) of 600-700 msec can be achieved in less time by using a zero delay and a shorter TP (400-500 msec).

Brain↗