Pure iterative reconstruction improves image quality in computed tomography of the abdomen and pelvis acquired at substantially reduced radiation doses in patients with active Crohn disease

Objective: We assessed diagnostic accuracy and image quality of modified protocol (MP) computed tomography (CT) of the abdomen and pelvis reconstructed using pure iterative reconstruction (IR) in patients with Crohn disease (CD). Methods: Thirty-four consecutive patients with CD were referred with suspected extramural complications. Two contemporaneous CT datasets were acquired in all patients: standard protocol (SP) and MP. The MP and SP protocols were designed to impart radiation exposures of 10% to 20% and 80% to 90% of routine abdominopelvic CT, respectively. The MP images were reconstructed with model-based IR (MBIR) and adaptive statistical IR (ASIR). Results: The MP-CT and SP-CT dose length product were 88 (58) mGy.cm (1.27 [0.87] mSv) and 303 [204] mGy.cm (4.8 [2.99] mSv), respectively (P < 0.001). Median diagnostic acceptability, spatial resolution, and contrast resolution were significantly higher and subjective noise scores were significantly lower on SP-ASIR 40 compared with all MP datasets. There was perfect clinical agreement between MP-MBIR and SP-ASIR 40 images for detection of extramural complications. Conclusions: Modified protocol CT using pure IR is feasible for assessment of active CD

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Feasibility of low-dose CT with model-based iterative image reconstruction in follow-up of patients with testicular cancer.

Purpose: We examine the performance of pure model-based iterative reconstruction with reduced-dose CT in follow-up of patients with early-stage testicular cancer. Methods: Sixteen patients (mean age 35.6 ± 7.4 years) with stage I or II testicular cancer underwent conventional dose (CD) and low-dose (LD) CT acquisition during CT surveillance. LD data was reconstructed with model-based iterative reconstruction (LD–MBIR). Datasets were objectively and subjectively analysed at 8 anatomical levels. Two blinded clinical reads were compared to gold-standard assessment for diagnostic accuracy. Results: Mean radiation dose reduction of 67.1% was recorded. Mean dose measurements for LD–MBIR were: thorax – 66 ± 11 mGy cm (DLP), 1.0 ± 0.2 mSv (ED), 2.0 ± 0.4 mGy (SSDE); abdominopelvic – 128 ± 38 mGy cm (DLP), 1.9 ± 0.6 mSv (ED), 3.0 ± 0.6 mGy (SSDE). Objective noise and signal-to-noise ratio values were comparable between the CD and LD–MBIR images. LD–MBIR images were superior (p < 0.001) with regard to subjective noise, streak artefact, 2-plane contrast resolution, 2-plane spatial resolution and diagnostic acceptability. All patients were correctly categorised as positive, indeterminate or negative for metastatic disease by 2 readers on LD–MBIR and CD datasets. Conclusions: MBIR facilitated a 67% reduction in radiation dose whilst producing images that were comparable or superior to conventional dose studies without loss of diagnostic utility

Feasibility of low-dose CT with model-based iterative image reconstruction in follow-up of patients with testicular cancer

Purpose: We examine the performance of pure model-based iterative reconstruction with reduced-dose CT in follow-up of patients with early-stage testicular cancer. Methods: Sixteen patients (mean age 35.6 ± 7.4 years) with stage I or II testicular cancer underwent conventional dose (CD) and low-dose (LD) CT acquisition during CT surveillance. LD data was reconstructed with model-based iterative reconstruction (LD–MBIR). Datasets were objectively and subjectively analysed at 8 anatomical levels. Two blinded clinical reads were compared to gold-standard assessment for diagnostic accuracy. Results: Mean radiation dose reduction of 67.1% was recorded. Mean dose measurements for LD–MBIR were: thorax – 66 ± 11 mGy cm (DLP), 1.0 ± 0.2 mSv (ED), 2.0 ± 0.4 mGy (SSDE); abdominopelvic – 128 ± 38 mGy cm (DLP), 1.9 ± 0.6 mSv (ED), 3.0 ± 0.6 mGy (SSDE). Objective noise and signal-to-noise ratio values were comparable between the CD and LD–MBIR images. LD–MBIR images were superior (p < 0.001) with regard to subjective noise, streak artefact, 2-plane contrast resolution, 2-plane spatial resolution and diagnostic acceptability. All patients were correctly categorised as positive, indeterminate or negative for metastatic disease by 2 readers on LD–MBIR and CD datasets. Conclusions: MBIR facilitated a 67% reduction in radiation dose whilst producing images that were comparable or superior to conventional dose studies without loss of diagnostic utility. Keywords: Testicular cancer, Radiation dose, Low-dose computed tomography, Iterative reconstruction, Model-based iterative reconstructio

Feasibility of low-dose CT with model-based iterative image reconstruction in follow-up of patients with testicular cancer.

Purpose: We examine the performance of pure model-based iterative reconstruction with reduced-dose CT in follow-up of patients with early-stage testicular cancer. Methods: Sixteen patients (mean age 35.6 ± 7.4 years) with stage I or II testicular cancer underwent conventional dose (CD) and low-dose (LD) CT acquisition during CT surveillance. LD data was reconstructed with model-based iterative reconstruction (LD–MBIR). Datasets were objectively and subjectively analysed at 8 anatomical levels. Two blinded clinical reads were compared to gold-standard assessment for diagnostic accuracy. Results: Mean radiation dose reduction of 67.1% was recorded. Mean dose measurements for LD–MBIR were: thorax – 66 ± 11 mGy cm (DLP), 1.0 ± 0.2 mSv (ED), 2.0 ± 0.4 mGy (SSDE); abdominopelvic – 128 ± 38 mGy cm (DLP), 1.9 ± 0.6 mSv (ED), 3.0 ± 0.6 mGy (SSDE). Objective noise and signal-to-noise ratio values were comparable between the CD and LD–MBIR images. LD–MBIR images were superior (p < 0.001) with regard to subjective noise, streak artefact, 2-plane contrast resolution, 2-plane spatial resolution and diagnostic acceptability. All patients were correctly categorised as positive, indeterminate or negative for metastatic disease by 2 readers on LD–MBIR and CD datasets. Conclusions: MBIR facilitated a 67% reduction in radiation dose whilst producing images that were comparable or superior to conventional dose studies without loss of diagnostic utility

The DNA sequence of the human X chromosome

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence