Objectives
To assess the image quality of T2-weighted (T2w) magnetic resonance imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T).
Materials & methods
Seventeen prostate ...cancer patients underwent T2w imaging at 7T with only an external transmit/receive array coil. Three radiologists independently scored images for image quality, visibility of anatomical structures, and presence of artefacts. Krippendorff’s alpha and weighted kappa statistics were used to assess inter-observer agreement. Visibility of prostate cancer lesions was assessed by directly linking the T2w images to the confirmed location of prostate cancer on histopathology.
Results
T2w imaging at 7T was achievable with ‘satisfactory’ (3/5) to ‘good’ (4/5) quality. Visibility of anatomical structures was predominantly scored as ‘satisfactory’ (3/5) and ‘good’ (4/5). If artefacts were present, they were mostly motion artefacts and, to a lesser extent, aliasing artefacts and noise. Krippendorff’s analysis revealed an α = 0.44 between three readers for the overall image quality scores. Clinically significant cancer lesions in both peripheral zone and transition zone were visible at 7T.
Conclusion
T2w imaging with satisfactory to good quality can be routinely acquired, and cancer lesions were visible in patients with prostate cancer at 7T using only an external transmit/receive body array coil.
Key Points
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Satisfactory to good T2-weighted image quality of the prostate is achievable at 7T.
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Periprostatic lipids appear hypo-intense compared to healthy peripheral zone tissue at 7T.
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Prostate cancer is visible on T2-weighted MRI at 7T.
To evaluate the feasibility to detect and delineate malignant breast lesions in human patients by chemical exchange saturation transfer (CEST) as an MR imaging technique without the need for contrast ...agent administration.
Six female patients referred for pre-surgical staging due to histologically confirmed breast cancer were examined with MR at 3 T. The routine breast protocol included T (2w), STIR, T (1w)-DCE and contrast-enhanced T (1w) imaging with SPAIR fat suppression. For CEST imaging, a 3D RF-spoiled gradient echo (GRE) sequence with an optimized saturation pulse train was applied. To assess the diagnostic value of the technique, CEST effects observed between frequency offsets of 1.2 to 1.8 ppm from the bulk water resonance were compared to pharmacokinetic parameter maps (k (ep)) obtained by DCE-MRI.
In 3 of 6 patients, regions with high CEST signal intensity correlated well with tumor areas as determined by DCE-MRI. Analysis of signal intensities from ROIs in tumor, fibroglandular, adipose, and muscle tissue revealed significantly higher CEST values in tumor tissue compared to fibroglandular tissue. The detection of lesions was equally well possible with DCE-MRI and CEST-MRI. In the three other patients, the tumor regions could not be delineated based on the CEST image due to artifacts, which were most likely caused by a high content of fat tissue within the ROIs.
The results of this initial feasibility study indicate a significant potential of CEST-MRI to discriminate cancer from fibroglandular tissue in the human breast by a CEST contrast generated by endogenous solute molecules.
A carboxylesterase derived from
Sulfolobus solfataricus
P1 was immobilized onto an epoxy-activated Sepharose resin
via
non-canonical amino acids. The immobilized enzyme exhibited heightened ...performance in organic solvents, recyclability, and stability at room temperature for over two years. The incorporation of a non-canonical amino acid afforded a high degree of control over the bioorthogonal immobilization reaction. These results indicate that the specificity conferred by genetic code expansion produces advantages in protein immobilization and broadens the utility of such proteins to non-biological settings.
A carboxylesterase derived from
Sulfolobus solfataricus
P1 was immobilized onto an epoxy-activated Sepharose resin
via
non-canonical amino acids.
Three approaches were used to study hybridization of complementary oligodeoxynucleotides by nonradiative fluorescence resonance energy transfer. (i) Fluorescein (donor) and rhodamine (acceptor) were ...covalently attached to the 5′ ends of complementary oligodeoxynucleotides of various lengths. Upon hybridization of the complementary oligodeoxy-nucleotides, energy transfer was detected by both a decrease in fluorescein emission intensity and an enhancement in rhodamine emission intensity. In all cases, fluorescein emission intensity was quenched by about 26% in the presence of unlabeled complement. Transfer efficiency at 5 degrees C decreased from 0.50 to 0.22 to 0.04 as the distance between donor and acceptor fluorophores in the hybrid increased from 8 to 12 to 16 nucleotides. Modeling of these hybrids as double helices showed that transfer efficiency decreased as the reciprocal of the sixth power of the donor-acceptor separation R, as predicted by theory with a corresponding R0 of 49 angstrom. (ii) Fluorescence resonance energy transfer was used to study hybridization of two fluorophore-labeled oligonucleotides to a longer, unlabeled oligodeoxynucleotide. Two 12-mers were prepared that were complementary to two adjacent sequences separated by four bases on a 29-mer. The adjacent 5′ and 3′ ends of the two 12-mers labeled with fluorescein and rhodamine exhibited a transfer efficiency of ≈ 0.60 at 5 degrees C when they both hybridized to the unlabeled 29-mer. (iii) An intercalating dye, acridine orange, was used as the donor fluorophore to a single rhodamine covalently attached to the 5′ end of one oligodeoxy-nucleotide in a 12-base-pair hybrid. Under these conditions, the transfer efficiency was ≈ 0.47 at 5 degrees C. These results establish that fluorescence modulation and nonradiative fluorescence resonance energy transfer can detect nucleic acid hybridization in solution. These techniques, with further development, may also prove useful for detecting and quantifying nucleic acid hybridization in living cells.
We have investigated the effect of sequence-specific antisense phosphorothioate-modified oligodeoxyribonucleotides (PS-ODNs) targeting different regions of each of the 30/32-kDa protein complex ...(antigen 85 complex) encoding genes on the multiplication of Mycobacterium tuberculosis. Single PS-ODNs to one of the three mycolyl transferase transcripts, added either once or weekly over the 6-wk observation period, inhibited bacterial growth by up to 1 log unit. A combination of three PS-ODNs specifically targeting all three transcripts inhibited bacterial growth by ≈2 logs; the addition of these PS-ODNs weekly for 6 wk was somewhat more effective than a one-time addition. Targeting the 5′ end of the transcripts was more inhibitory than targeting internal sites; the most effective PS-ODNs and target sites had minimal or no secondary structure. The effect of the PS-ODNs was specific, as mismatched PS-ODNs had little or no inhibitory activity. The antisense PS-ODNs, which were highly stable in M. tuberculosis cultures, specifically blocked protein expression by their gene target. PS-ODNs targeting the transcript of a related 24-kDa protein (mpt51) had little inhibitory effect by themselves and did not increase the effect of PS-ODNs against the three members of the 30/32-kDa protein complex. The addition of PS-ODNs against the transcripts of glutamine synthetase I (glnA1) and alanine racemase (alr) modestly increased the inhibitory efficacy of the 30/32-kDa protein complex-specific PS-ODNs to ≈2.5 logs. This study shows that the three mycolyl transferases are highly promising targets for antituberculous therapy by using antisense or other antimicrobial technologies.
New antibiotics to combat the emerging pandemic of drug-resistant strains of Mycobacterium tuberculosis are urgently needed. We have investigated the effects on M. tuberculosis of ...phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODNs) against the mRNA of glutamine synthetase, an enzyme whose export is associated with pathogenicity and with the formation of a poly-L-glutamate/glutamine cell wall structure. Treatment of virulent M. tuberculosis with 10 μ M antisense PS-ODNs reduced glutamine synthetase activity and expression by 25-50% depending on whether one, two, or three different PS-ODNs were used and the PS-ODNs' specific target sites on the mRNA. Treatment with PS-ODNs of a recombinant strain of Mycobacterium smegmatis expressing M. tuberculosis glutamine synthetase selectively inhibited the recombinant enzyme but not the endogenous enzyme for which the mRNA transcript was mismatched by 2-4 nt. Treatment of M. tuberculosis with the antisense PS-ODNs also reduced the amount of poly-L-glutamate/glutamine in the cell wall by 24%. Finally, treatment with antisense PS-ODNs reduced M. tuberculosis growth by 0.7 logs (1 PS-ODN) to 1.25 logs (3 PS-ODNs) but had no effect on the growth of M. smegmatis, which does not export glutamine synthetase nor possess the poly-L-glutamate/glutamine (P-L-glx) cell wall structure. The experiments indicate that the antisense PS-ODNs enter the cytoplasm of M. tuberculosis and bind to their cognate targets. Although more potent ODN technology is needed, this study demonstrates the feasibility of using antisense ODNs in the antibiotic armamentarium against M. tuberculosis.
Survival in patients after surgical resection of pulmonary metastases correlates with the complete resection of all metastatic deposits. The purpose of this study was to evaluate the additional value ...of helical CT to see whether the slice thickness and the reading environment was a factor determining the accuracy of helical scans.
Between 2004 and 2007, 93 patients (62 men, 31 women) underwent complete resection of pulmonary metastases by open thoracotomy. A total of 125 thoracotomies were performed with manual palpation of the involved lung. We retrospectively examined the helical CT findings obtained using a 5-mm slice thickness in a routine preoperative analysis, and within this study a second reading was performed independently, using 3-mm slice thickness image sets. The CT images were evaluated in a consensus between two radiologists.
Computed tomography scanning was performed a median of 12 days before thoracotomy (range 1-121 days). Analysis of helical CT in 5-mm slice thickness detected metastases with a sensitivity of 83.7 % whereas a 3-mm slice thickness had a sensitivity of 88.8 %. There were statistically significantly more lesions using helical CT and a 3-mm slice thickness technique than with the 5-mm slice thickness technique, compared to the surgical results ( P = 0.002). This was also found with regard to nodules which were finally histologically confirmed as lung metastases ( P = 0.014).
We conclude that a reduced slice thickness may have an important positive impact on the treatment and outcome of patients with pulmonary metastases. The use of 3-mm slice thickness helical CT may raise the sensitivity for pulmonary metastases detection compared to 5-mm images, but the rate of false positive results may also increase.
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