Legionella pneumophila macrophage infectivity potentiator protein appendage domains modulate protein dynamics and inhibitor binding.

Macrophage infectivity potentiator (MIP) proteins are widespread in human pathogens including Legionella pneumophila, the causative agent of Legionnaires' disease and protozoans such as Trypanosoma cruzi. All MIP proteins contain a FKBP (FK506 binding protein)-like prolyl-cis/trans-isomerase domain that hence presents an attractive drug target. Some MIPs such as the Legionella pneumophila protein (LpMIP) have additional appendage domains of mostly unknown function. In full-length, homodimeric LpMIP, the N-terminal dimerization domain is linked to the FKBP-like domain via a long, free-standing stalk helix. Combining X-ray crystallography, NMR and EPR spectroscopy and SAXS, we elucidated the importance of the stalk helix for protein dynamics and inhibitor binding to the FKBP-like domain and bidirectional crosstalk between the different protein regions. The first comparison of a microbial MIP and a human FKBP in complex with the same synthetic inhibitor was made possible by high-resolution structures of LpMIP with a [4.3.1]-aza-bicyclic sulfonamide and provides a basis for designing pathogen-selective inhibitors. Through stereospecific methylation, the affinity of inhibitors to L. pneumophila and T. cruzi MIP was greatly improved. The resulting X-ray inhibitor-complex structures of LpMIP and TcMIP at 1.49 and 1.34 Å, respectively, provide a starting point for developing potent inhibitors against MIPs from multiple pathogenic microorganisms.

The value of MRI STIR signal intensity on return to play prognosis and reinjury risk estimation in athletes with acute hamstring injuries.

OBJECTIVES: Previous studies have shown low to moderate evidence for a variety of magnetic resonance imaging (MRI) features as prognostic factors in athletes with hamstring injuries. Short-tau inversion recovery (STIR) signal intensity has not yet been investigated for assessing the prognosis of acute muscle injuries. Our aim was to explore the relationship between MRI STIR signal intensity and time to return to play (RTP) and to investigate the association between MRI STIR and reinjury risk in athletes with acute hamstring injuries. STUDY DESIGN: Case-control study. METHODS: We used MRI STIR to measure intramuscular signal intensity in patients with clinically diagnosed hamstring injuries at two time points: at injury and RTP. At injury, we calculated the association of MRI STIR signal intensity with the time to RTP and reinjury risk. At RTP, the association of MRI STIR signal intensity and reinjury risk and the change in MRI STIR signal intensity over time on reinjury risk was evaluated. RESULTS: 51 patients were included. We found increased MRI STIR signal intensity: (1) at time of injury not to be associated with time to RTP, (2) at time of injury to be associated with a slightly lower risk for reinjury: odds 0.986 (0.975-0.998, p=0.02) and (3) at RTP not to be associated with reinjury risk. (4) We found no association between the change in MRI STIR signal intensity over time and reinjury risk. CONCLUSION: Increased MRI STIR signal intensity at injury has no value in time to RTP prognosis, but is associated with a reduced reinjury risk.

The road to optimal acceleration of Dixon imaging and quantitative T2-mapping in the ankle using compressed sensing and parallel imaging.

OBJECTIVE: This study aimed to find the optimal acceleration factor achievable with CS-SENSE for a clinical ankle protocol while maintaining comparable image quality. METHODS: We explored the optimal acceleration achievable with factor CS-SENSE, for an ankle protocol with T2-weighted, PD-weighted TSE-Dixon (coronal, axial and sagittal) and T2-mapping (sagittal) sequences, on a 3 T MRI-scanner. This study contained three steps: (1) phantom test, (2) pilot test on healthy volunteers, (3) anatomical assessment on a cohort of healthy volunteers and a quantitative analysis. CS-SENSE images (acceleration factors between 2.0× and 12.0×) were compared to reference SENSE images (acceleration factor 2.0×). Three blinded radiologists evaluated the image quality and provided an anatomical assessment using a five-point Likert scale of 25 anatomical regions. RESULTS: The total acquisition time of the TSE-Dixon sequence was reduced by 45 % from 13'38″ to 7'37″ (acceleration factor between 3.6× and 4.0×), the T2-mapping scan time was reduced by 31 % from 5'28″ to 3'47″ (acceleration factor of 3.0×), while maintaining comparable image quality. The results from the anatomical assessment of SENSE 2.0× versus CS-SENSE 3.6× were comparable in 88.7 % as shown by the 5-point Likert scale measurements. The T2-relaxation measurements had a good correlation of ρ = 0.7 between SENSE and CS-SENSE. CONCLUSION: We found an optimum acceleration factor with CS-SENSE between 3.6× and 4.0× for TSE-Dixon and 3.0× for T2-mapping sequences in a clinical MR imaging protocol of the ankle. The total scan time was reduced by 41 % while maintaining adequate image quality.

SPECT scatter modelling in non-uniform attenuating objects.

SPECT quantitation and image contrast are degraded by photon scatter. Water equivalent depths (WEDs) have been used by several investigators to model scatter responses in non-uniform attenuators. The drawback of this approach is the occurrence of undesired fluctuations in the shape of the scatter responses, as is shown by measurements. An improvement of the WED method is presented, based on the assumption that only a part of the scattering object (the region in the 'scatter cone') contributes significantly to the detected scatter events. The remaining part of the object is treated as a uniform medium. The extension of the WED method with extra-conical invariance (WEDECI) is evaluated by projection measurements of a phantom with a 99mTc source. Shapes of scatter responses predicted by the WEDECI method are found to agree better with the measurements than those predicted by conventional WEDs.