Nocardiosis in solid-organ transplant recipients: spectrum of imaging findings.

Nocardiosis is an infrequent but severe infection that primarily affects the lung and thence is able to produce disseminated disease. Prompt diagnosis of pulmonary and disseminated nocardiosis is of utmost importance in solid-organ transplant recipients to reduce mortality. Knowledge of the different radiological manifestations in the appropriate clinical setting is key to successful management of these patients. The aim of this review is to describe the radiological features of nocardiosis in immunosuppressed patients, particularly in solid-organ transplant recipients.

Feasibility of computed tomography based thermometry during interstitial laser heating in bovine liver.

OBJECTIVES: To assess the feasibility of computed tomography (CT) based thermometry during interstitial laser heating in the bovine liver. METHODS: Four freshly exercised cylindrical blocks of bovine tissue were heated using a continuous laser of Nd:YAG (wavelength: 1064 nm, active length: 30 mm, power: 10-30 W). All tissues were imaged at least once before and 7 times during laser heating using CT and temperatures were simultaneously measured with 5 calibrated thermal sensors. The dependency of the average CT numbers as a function of temperature was analysed with regression analysis and a CT thermal sensitivity was derived. RESULTS: During laser heating, the growing hypodense area was observed around the laser source and that area showed an increase as a function of time. The formation of hypodense area was caused by declining in CT numbers at increasing temperatures. The regression analysis showed an inverse linear dependency between temperature and average CT number with -0.65 ± 0.048 HU/°C (R(2) = 0.75) for the range of 18-85°C in bovine liver. CONCLUSIONS: The non-invasive CT based thermometry during interstitial laser heating is feasible in the bovine liver. CT based thermometry could be further developed and may be of potential use during clinical LITT of the liver.

Strategies for scatter correction in dual source CT.

PURPOSE: Dual source CT (DSCT) systems utilize two measurement systems (A) and (B) offset by about 90 degrees. A special challenge in DSCT is cross-scattered radiation, i.e., scattered radiation from x-ray tube (B) detected in detector (A) and vice versa. Cross-scattered radiation can produce artifacts and degrade the contrast-to-noise ratio (CNR) of the images. Correction algorithms are mandatory to mitigate the negative effects of cross-scattered radiation. The purpose of this work is to describe and evaluate different methods for cross-scatter correction in DSCT. METHODS: The authors present two techniques for cross-scatter correction in DSCT. The first technique (1) is model-based. Assuming that cross-scatter is predominantly surface scatter, adequate knowledge about the surface of the scattering object is sufficient to describe the magnitude and distribution of cross-scatter. The relevant surface information is derived from an analysis of the raw-data sinogram during the CT-scan. The correction is performed by a table look-up into previously measured and stored cross-scatter distributions for a variety of objects with different surface characteristics. The second technique (2) is measurement-based. Dedicated sensors outside the penumbra of the fan beam in the z direction on both detectors (A) and (B) are used for an online measurement of both cross-scattered and forward scattered radiation during the CT-scan. In addition to the two scatter-correction techniques, the authors describe a low-pass filter method for the scatter-correction term with the goal to improve the CNR of the corrected images. This filter can be applied to both model-based (1) and measurement-based (2) scatter correction. Both scatter-correction techniques (1) and (2) are quantitatively assessed and the performance of the low-pass filter method is evaluated using DSCT data of phantoms (water cylinders and anthropomorphic phantoms) and DSCT patient scan data. RESULTS: Both scatter-correction techniques restore image contrasts and reduce cross-scatter induced artifacts in DSCT images. The measurement-based technique results in higher CNR than the model-based technique if the proposed low-pass filtering of the scatter-correction term is applied. Low-pass filtering improves the CNR of cross-scatter-correction approaches beyond the limits published in the literature [Engel et al., "X-ray scattering in single- and dual-source CT," Med. Phys. 35(1), 318-332 (2008)]. CONCLUSIONS: Both model-based and measurement-based scatter correction can mitigate the negative effects of cross-scatter in DSCT. The application of low-pass filtering to the scatter-correction term improves the CNR whenever the ratio of scattered radiation to total signal is high, as in larger patients.

Image reconstruction and image quality evaluation for a dual source CT scanner.

The authors present and evaluate concepts for image reconstruction in dual source CT (DSCT). They describe both standard spiral (helical) DSCT image reconstruction and electrocardiogram (ECG)-synchronized image reconstruction. For a compact mechanical design of the DSCT, one detector (A) can cover the full scan field of view, while the other detector (B) has to be restricted to a smaller, central field of view. The authors develop an algorithm for scan data completion, extrapolating truncated data of detector (B) by using data of detector (A). They propose a unified framework for convolution and simultaneous 3D backprojection of both (A) and (B) data, with similar treatment of standard spiral, ECG-gated spiral, and sequential (axial) scan data. In ECG-synchronized image reconstruction, a flexible scan data range per measurement system can be used to trade off temporal resolution for reduced image noise. Both data extrapolation and image reconstruction are evaluated by means of computer simulated data of anthropomorphic phantoms, by phantom measurements and patient studies. The authors show that a consistent filter direction along the spiral tangent on both detectors is essential to reduce cone-beam artifacts, requiring truncation of the extrapolated (B) data after convolution in standard spiral scans. Reconstructions of an anthropomorphic thorax phantom demonstrate good image quality and dose accumulation as theoretically expected for simultaneous 3D backprojection of the filtered (A) data and the truncated filtered (B) data into the same 3D image volume. In ECG-gated spiral modes, spiral slice sensitivity profiles (SSPs) show only minor dependence on the patient's heart rate if the spiral pitch is properly adapted. Measurements with a thin gold plate phantom result in effective slice widths (full width at half maximum of the SSP) of 0.63-0.69 mm for the nominal 0.6 mm slice and 0.82-0.87 mm for the nominal 0.75 mm slice. The visually determined through-plane (z axis) spatial resolution in a bar pattern phantom is 0.33-0.36 mm for the nominal 0.6 mm slice and 0.45 mm for the nominal 0.75 mm slice, again almost independent of the patient's heart rate. The authors verify the theoretically expected temporal resolution of 83 ms at 330 ms gantry rotation time by blur free images of a moving coronary artery phantom with 90 ms rest phase and demonstrate image noise reduction as predicted for increased reconstruction data ranges per measurement system. Finally, they show that the smoothness of the transition between image stacks acquired in different cardiac cycles can be efficiently controlled with the proposed approach for ECG-synchronized image reconstruction.

Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia: a case-control study.

We genotyped six folate metabolic pathway genes for 11 polymorphisms in 460 cases of childhood acute lymphoblastic leukemia (ALL) and 552 ethnically matched controls. None of the polymorphisms except the 66A>G (I22M) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene showed any effect on disease risk. The carriers of the G-allele were associated with a marginal decreased risk of ALL (gender-adjusted global P=0.03; multiple-testing corrected P=0.25). Analysis of four polymorphisms in the MTRR gene showed statistically significant differences in haplotype distribution between cases and controls (global P<0.0001). The haplotypes GCAC (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4-0.6) and ATAC (OR 0.5, 95% CI 0.3-0.6) were associated with a reduced risk and the haplotypes ACAC (OR 2.3, 95% CI 1.8-2.9) and GTAC (OR 1.8, 95% CI 1.4-2.3) with an increased risk. The genotype-combination analyses indicated that the best model stratifies cases and controls based on the 66A>G and the 524C>T polymorphisms in the MTRR gene (global P=0.03). Our results suggest that, besides a weak association of childhood ALL with the 66A>G polymorphism, haplotypes within the MTRR gene may, in part, account for population-based differences in risk.

Acute lymphoblastic leukemia with t(4;11) in children 1 year and older: The 'big sister' of the infant disease?

The t(4;11)-positive acute lymphoblastic leukemia (ALL) is a rare disease in children above the age of 1 year. We studied the clinical and biological characteristics in 32 consecutively diagnosed childhood cases (median age 10.0 years, range 1.0-17.1 years). Immunophenotyping revealed a pro-B and a pre-B stage in 24 and eight cases, respectively. IGH genes were rearranged in 84% of leukemias with a predominance of incomplete DJ(H) joints. Whereas IGK-Kde and TCRD rearrangements were rare, TCRG rearrangements were present in 50% of cases and involved mainly Vgamma11 or Vgamma9 together with a Jgamma1.3./2.3 gene segment, an unusual combination among t(4;11)-negative B-cell precursor ALL. Oligoclonality was found in about 30% as assessed by heterogeneous IGH and TCRG rearrangements. Our data are in line with transformation of a precursor cell at an early stage of B-cell development but retaining the potential to differentiate to the pre-B cell stage in vivo. Although a distinct difference between infant and older childhood cases with t(4;11) became evident, no age-related biological features were found within the childhood age group. In contrast to infants with t(4;11)-positive ALL, childhood cases had a relatively low cumulative incidence of relapse of 25% at 3.5 years with BFM-based high-risk protocols.

Optimization of PCR-based minimal residual disease diagnostics for childhood acute lymphoblastic leukemia in a multi-center setting.

Minimal residual disease (MRD) diagnostics is used for treatment stratification in childhood acute lymphoblastic leukemia. We aimed to identify and solve potential problems in multicenter MRD studies to achieve and maintain consistent results between the AIEOP/BFM ALL-2000 MRD laboratories. As the dot-blot hybridization method was replaced by the real-time quantitative polymerase chain reaction (RQ-PCR) method during the treatment protocol, special attention was given to the comparison of MRD data obtained by both methods and to the reproducibility of RQ-PCR data. Evaluation of all key steps in molecular MRD diagnostics identified several pitfalls that resulted in discordant MRD results. In particular, guidelines for RQ-PCR data interpretation appeared to be crucial for obtaining concordant MRD results. The experimental variation of the RQ-PCR was generally less than three-fold, but logically became larger at low MRD levels below the reproducible sensitivity of the assay (<10(-4)). Finally, MRD data obtained by dot-blot hybridization were comparable to those obtained by RQ-PCR analysis (r(2)=0.74). In conclusion, MRD diagnostics using RQ-PCR analysis of immunoglobulin/T-cell receptor gene rearrangements is feasible in multicenter studies but requires standardization; particularly strict guidelines for interpretation of RQ-PCR data are required. We further recommend regular quality control for laboratories performing MRD diagnostics in international treatment protocols.

Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

Lymphoproliferations are generally diagnosed via histomorphology and immunohistochemistry. Although mostly conclusive, occasionally the differential diagnosis between reactive lesions and malignant lymphomas is difficult. In such cases molecular clonality studies of immunoglobulin (Ig)/T-cell receptor (TCR) rearrangements can be useful. Here we address the issue of clonality assessment in 106 histologically defined reactive lesions, using the standardized BIOMED-2 Ig/TCR multiplex polymerase chain reaction (PCR) heteroduplex and GeneScan assays. Samples were reviewed nationally, except 10% random cases and cases with clonal results selected for additional international panel review. In total 75% (79/106) only showed polyclonal Ig/TCR targets (type I), whereas another 15% (16/106) represent probably polyclonal cases, with weak Ig/TCR (oligo)clonality in an otherwise polyclonal background (type II). Interestingly, in 10% (11/106) clear monoclonal Ig/TCR products were observed (types III/IV), which prompted further pathological review. Clonal cases included two missed lymphomas in national review and nine cases that could be explained as diagnostically difficult cases or probable lymphomas upon additional review. Our data show that the BIOMED-2 Ig/TCR multiplex PCR assays are very helpful in confirming the polyclonal character in the vast majority of reactive lesions. However, clonality detection in a minority should lead to detailed pathological review, including close interaction between pathologist and molecular biologist.

Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data.

Most modern treatment protocols for acute lymphoblastic leukaemia (ALL) include the analysis of minimal residual disease (MRD). To ensure comparable MRD results between different MRD-polymerase chain reaction (PCR) laboratories, standardization and quality control are essential. The European Study Group on MRD detection in ALL (ESG-MRD-ALL), consisting of 30 MRD-PCR laboratories worldwide, has developed guidelines for the interpretation of real-time quantitative PCR-based MRD data. The application of these guidelines ensures identical interpretation of MRD data between different laboratories of the same MRD-based clinical protocol. Furthermore, the ESG-MRD-ALL guidelines will facilitate the comparison of MRD data obtained in different treatment protocols, including those with new drugs.

Benign transient hyperphosphatasemia associated with Epstein-Barr virus enteritis in a pediatric liver transplant patient: a case report.

Transient hyperphosphatasemia was found in a 3-year-old male liver transplant recipient. The condition was associated with diarrheal disease due to the Epstein-Barr virus (EBV). Immunosuppression was tapered and valganciclovir prescribed for 3 months, after which the diarrhea resolved and the EBV polymerase chain reaction assays became negative. After 6 months, alkaline phosphatase levels normalized. Isolated elevation of alkaline phosphatase in conjunction with enteric infection is a rare condition. No further diagnostic or therapeutic interventions except treatment of the underlying infection are needed, as this has been shown to be a benign, transient condition.

Novel ultrahigh resolution data acquisition and image reconstruction for multi-detector row CT.

We present and evaluate a special ultrahigh resolution mode providing considerably enhanced spatial resolution both in the scan plane and in the z-axis direction for a routine medical multi-detector row computed tomography (CT) system. Data acquisition is performed by using a flying focal spot both in the scan plane and in the z-axis direction in combination with tantalum grids that are inserted in front of the multi-row detector to reduce the aperture of the detector elements both in-plane and in the z-axis direction. The dose utilization of the system for standard applications is not affected, since the grids are moved into place only when needed and are removed for standard scanning. By means of this technique, image slices with a nominal section width of 0.4 mm (measured full width at half maximum=0.45 mm) can be reconstructed in spiral mode on a CT system with a detector configuration of 32 x 0.6 mm. The measured 2% value of the in-plane modulation transfer function (MTF) is 20.4 lp/cm, the measured 2% value of the longitudinal (z axis) MTF is 21.5 lp/cm. In a resolution phantom with metal line pair test patterns, spatial resolution of 20 lp/cm can be demonstrated both in the scan plane and along the z axis. This corresponds to an object size of 0.25 mm that can be resolved. The new mode is intended for ultrahigh resolution bone imaging, in particular for wrists, joints, and inner ear studies, where a higher level of image noise due to the reduced aperture is an acceptable trade-off for the clinical benefit brought about by the improved spatial resolution.

Dual Energy CT Kidney Stone Differentiation in Photon Counting Computed Tomography.

This study evaluates the capabilities of a whole-body photon counting CT system to differentiate between four common kidney stone materials, namely uric acid (UA), calcium oxalate monohydrate (COM), cystine (CYS),and apatite (APA) ex vivo. Two different x-ray spectra (120 kV and 140 kV) were applied and two acquisition modes were investigated; The macro-mode generates two energy threshold based image-volumes and two energy bin based image-volumes. In the chesspattern-mode, however, four energy thresholds are applied. A virtual low energy image, as well as a virtual high energy image are derived from initial threshold-based images, while considering their statistically correlated nature. The energy bin based images of the macro-mode, as well as the virtual low and high energy image of the chesspattern-mode serve as input for our dual energy evaluation. The dual energy ratio of the individually segmented kidney stones were utilized to quantify the discriminability of the different materials. The dual energy ratios of the two acquisition modes showed high correlation for both applied spectra. Wilcoxon-rank sum tests and the evaluation of the area under the receiver operating characteristics curves suggest that the UA kidney stones are best differentiable from all other materials (AUC = 1.0), followed by CYS (AUC ≈ 0.9 compared against COM and APA). COM and APA, however, are hardly distinguishable (AUC between 0.63 and 0.76). The results hold true for the measurements of both spectra and both acquisition modes.

Rapid and reliable quantification of minimal residual disease in acute lymphoblastic leukemia using rearranged immunoglobulin and T-cell receptor loci by LightCycler technology.

The detection of minimal residual disease (MRD) using immunoglobulin and T-cell receptor (TCR) rearrangements as PCR targets provides important prognostic information on the in vivo effectiveness of treatment in acute lymphoblastic leukemia (ALL). Here we report on the real-time quantification of MRD in 25 ALL patients using LightCycler technology. We designed and adapted allele-specific oligonucleotide (ASO)-PCR protocols that enabled the detection of >90% of the IGH, IGK, TCRD, and TCRG rearrangements observed in ALL patients. In all patients, at least two suitable markers could be identified (average, 3.4 markers/patient). We applied ASO-PCR with 35 immunoglobulin and TCR rearrangements (11 IGH, 6 IGK, 12 TCRG, and 6 TCRD) and compared the sensitivity and practicability of the LightCycler strategy with conventional ASO-PCR on a block thermocycler followed by quantification with gel electrophoresis. The LightCycler measured leukemia-specific PCR products at each cycle (real-time) by staining the PCR product with the DNA-binding dye SYBR Green I. LightCycler technology showed a higher sensitivity than the conventional method in eight cases, whereas the sensitivity of the other markers matched exactly. The detection level varied between 10(-4) and 10(-6) leukemic cells. Furthermore, we determined the MRD status of 27 bone marrow follow-up samples from 15 ALL patients by both methods and revealed comparable results. However, the LightCycler also allowed accurate quantification in samples containing relatively high levels (>10(-3)) of residual leukemia cells. The conventional ASO-PCR technique comprises various laborious and time-consuming PCR experiments and post-PCR steps to determine the number of cycles with the optimal linearity and sensitivity of the PCR. Real-time quantification through LightCycler technology obviates these post-PCR steps, provides the highest sensitivity via software analysis, and therefore represents a rapid, reliable, sensitive, and cost-effective technique for the routine monitoring of MRD in ALL patients.

Image reconstruction and image quality evaluation for a 64-slice CT scanner with z-flying focal spot.

We present a theoretical overview and a performance evaluation of a novel z-sampling technique for multidetector row CT (MDCT), relying on a periodic motion of the focal spot in the longitudinal direction (z-flying focal spot) to double the number of simultaneously acquired slices. The z-flying focal spot technique has been implemented in a recently introduced MDCT scanner. Using 32 x 0.6 mm collimation, this scanner acquires 64 overlapping 0.6 mm slices per rotation in its spiral (helical) mode of operation, with the goal of improved longitudinal resolution and reduction of spiral artifacts. The longitudinal sampling distance at isocenter is 0.3 mm. We discuss in detail the impact of the z-flying focal spot technique on image reconstruction. We present measurements of spiral slice sensitivity profiles (SSPs) and of longitudinal resolution, both in the isocenter and off-center. We evaluate the pitch dependence of the image noise measured in a centered 20 cm water phantom. To investigate spiral image quality we present images of an anthropomorphic thorax phantom and patient scans. The full width at half maximum (FWHM) of the spiral SSPs shows only minor variations as a function of the pitch, measured values differ by less than 0.15 mm from the nominal values 0.6, 0.75, 1, 1.5, and 2 mm. The measured FWHM of the smallest slice ranges between 0.66 and 0.68 mm at isocenter, except for pitch 0.55 (0.72 mm). In a centered z-resolution phantom, bar patterns up to 15 lp/cm can be visualized independent of the pitch, corresponding to 0.33 mm longitudinal resolution. 100 mm off-center, bar patterns up to 14 lp/cm are visible, corresponding to an object size of 0.36 mm that can be resolved in the z direction. Image noise for constant effective mAs is almost independent of the pitch. Measured values show a variation of less than 7% as a function of the pitch, which demonstrates correct utilization of the applied radiation dose at any pitch. The product of image noise and square root of the slice width (FWHM of the respective SSP) is the same constant for all slices except 0.6 mm. For the thinnest slice, relative image noise is increased by 17%. Spiral windmill-type artifacts are effectively suppressed with the z-flying focal spot technique, which has the potential to maintain a low artifact level up to pitch 1.5, in this way increasing the maximum volume coverage speed that can be clinically used.

High incidence and unique features of antigen receptor gene rearrangements in TEL-AML1-positive leukemias.

The t(12;21) translocation resulting in the TEL-AML1 gene fusion is found in 25% of childhood B-cell precursor (BCP) acute lymphoblastic leukemias (ALL). Since TEL-AML1 has been reported to induce cell cycle retardation and thus may influence somatic recombination, we analyzed 214 TEL-AML1-positive ALL by PCR for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. As a control group, 174 childhood BCP ALL without a TEL-AML1 were used. The majority of TEL-AML1-positive leukemias had a higher number of Ig/TCR rearrangements than control ALL. They also had a more mature immunogenotype characterized by their high frequency of complete IGH, IGK-Kde, and TCRG rearrangements. While IGK-Kde and TCRG were more frequently rearranged on both alleles at higher age, IGH and TCRD rearrangements decreased in their incidence along with a decrease in biallelic IGH rearrangements. This suggests that the recombination process continues in these leukemias leading to ongoing rearrangements and possibly also deletions of antigen receptor genes. We here provide first evidence that somatic recombination of antigen receptor genes is affected by the TEL-AML1 fusion, and that further age-related differences are probably caused by the longer latency period of the prenatally initiated TEL-AML1-positive leukemias in older children.

Novel iterative reconstruction method with optimal dose usage for partially redundant CT-acquisition.

In CT imaging, a variety of applications exist which are strongly SNR limited. However, in some cases redundant data of the same body region provide additional quanta. Examples in dual energy CT, the spatial resolution has to be compromised to provide good SNR for material decomposition. However, the respective spectral dataset of the same body region provides additional quanta which might be utilized to improve SNR of each spectral component. Perfusion CT is a high dose application, and dose reduction is highly desirable. However, a meaningful evaluation of perfusion parameters might be impaired by noisy time frames. On the other hand, the SNR of the average of all time frames is extremely high.In redundant CT acquisitions, multiple image datasets can be reconstructed and averaged to composite image data. These composite image data, however, might be compromised with respect to contrast resolution and/or spatial resolution and/or temporal resolution. These observations bring us to the idea of transferring high SNR of composite image data to low SNR 'source' image data, while maintaining their resolution.It has been shown that the noise characteristics of CT image data can be improved by iterative reconstruction (Popescu et al 2012 Book of Abstracts, 2nd CT Meeting (Salt Lake City, UT) p 148). In case of data dependent Gaussian noise it can be modelled with image-based iterative reconstruction at least in an approximate manner (Bruder et al 2011 Proc. SPIE 7961 79610J). We present a generalized update equation in image space, consisting of a linear combination of the previous update, a correction term which is constrained by the source image data, and a regularization prior, which is initialized by the composite image data. This iterative reconstruction approach we call bimodal reconstruction (BMR). Based on simulation data it is shown that BMR can improve low contrast detectability, substantially reduces the noise power and has the potential to recover spatial resolution of the source image data.For different CT applications: dual energy imaging, liver imaging, spiral imaging, cardiac imaging, we show that SNR can efficiently be transferred from the composite image to the source image data at constant patient dose, while maintaining resolution properties of the source data.

Determination of the Middle Cerebral Artery Occlusion Length in Acute Stroke: Contribution of 4D CT Angiography and Importance for Thrombolytic Efficacy Prediction.

PURPOSE: To assess the benefit of 4D-CT angiography (4D-CTA) in determination and precise measurement of middle cerebral artery (MCA) occlusion in comparison to CTA. Possible relationship of measured occlusion lengths with recanalization after intravenous thrombolysis was analysed as a second objective. METHODS: Detailed evaluation of complete MCA occlusions in 80 patients before intravenous thrombolysis using temporal maximum intensity projection (tMIP) dataset, calculated from 4D-CTA and conventional single-phase CTA was performed. Further, manual measurement technique was compared to results of semiautomatic procedure (vessel analysis) as reference. Statistical analysis of correlation between MCA occlusion length and IVT efficacy (24 h recanalization rate according modified Thrombolysis In Myocardial Infarction criteria-mTIMI) was performed. RESULTS: The distal end of occlusion was identified in all patients using tMIP, but only in 48 patients (60%) using CTA. The manual measurement method was not statistically different and well correlated with reference tMIP-vessel analysis. (15.4 vs. 16.3 mm; p = 0.434; r = 97). In measurable occlusions by CTA, no significant difference was proved in manually measured lengths using tMIP and CTA (14.5 vs. 13.3 mm; p = 0.089). Favorable recanalization (mTIMI 2-3) was achieved in 37 patients (47%). Length of occlusion in M1 segment (p = 0.002) and M2 segment involvement (p = 0.017) were proved as independent negative predictors of recanalization. Using receiver operating characteristics analysis, the cutoff length of the M1 segment occlusion for favorable recanalization was found to be 12 mm. CONCLUSION: The feasibility of MCA occlusion assessment using tMIP datasets and benefit over conventional CTA were confirmed. The manual measurement method was proved as feasible and simple with good correlation to reference semiautomatic analysis. The significant correlation of the MCA occlusion length and early recanalization was found. The length of 12 mm was recognized as cut-off length for favorable recanalization.

Association between the 5' UTR variant C178T of the serotonin receptor gene HTR3A and bipolar affective disorder.

Serotonin receptor type 3 is a ligand-gated ion channel implicated in behavioural disorders. Our objective was to identify nucleotide variants in a specific portion of the 5' region of the serotonin receptor gene (HTR3A) containing upstream open reading frames (uORFs) and to investigate their effect on bipolar disease. Mutations in uORFs have been recently shown to cause disease by changing expression on the translational level. We identified one polymorphism, C195T, and one missense mutation, C178T (Pro16Ser) within an upstream open reading frame. No significant association was found between the C195T polymorphism and bipolar affective disorder. A significant association was, however, found between the variant C178T in 156 patients with bipolar disorder compared to 156 healthy controls (P = 0.00016). To investigate the relevance of this variant on gene expression, luciferase reporter constructs containing the C178T (Pro16Ser) allele were established and compared to the C178T plus C195T and wild-type alleles. Reporter constructs containing the C178T (Pro16Ser) allele drove 245% and 138% expression compared to the wild-type allele. These findings show that the C178T(Pro16Ser) variant in HTR3A may represent a functional variant and affect the susceptibility to bipolar disorder.

An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase.

Interferon gamma induces expression of a protein termed IFP 53 according to its molecular weight of 53 kDa. IFP 53 shows significant sequence homology to rabbit peptide chain release factor as well as to bovine tryptophanyl-tRNA synthetase. IFP 53 has been shown to possess release factor activity for the UGA stop codon. We demonstrate here, by using a recombinant IFP 53 fusion protein, that IFP 53 tryptophanylates tRNA. These data indicate that IFP 53 is a protein with two activities: peptide chain termination and aminoacylation.

Individually adapted examination protocols for reduction of radiation exposure in chest CT.

RATIONALE AND OBJECTIVES: To develop a simple directive for the reduction of radiation exposure without loss of diagnostic information in routine chest CT examinations. METHODS: Two hundred fifty adult patients (164 male, 86 female) were entered into a prospective trial. All examinations were performed with a multislice CT technique (Somatom Volume Zoom, Siemens). Four groups of 50 patients each were scanned with patient-related specific parameters: individual mA-s values were derived from the estimated body weight: kilograms + 10, +/- 0, - 10, and - 20 mAs. The results were compared with those of 50 patients who were examined by a standard chest protocol by using the parameters 120 mAs and 140 kV. All other parameters including the tube voltage were kept constant. Subjective image quality was rated on a three-point scale: 1 = excellent, 2 = fair, 3 = nondiagnostic. In addition, objective criteria based on signal-to-noise measurements were assessed by using a region-of-interest methodology. RESULTS: Image quality was sufficient in all cases. Mean subjective gradings of image quality, based on soft-tissue window settings, were 1.1 for the 120-mAs protocol, 1.1 for the (body weight [kg] + 10) mAs protocol, 1.1 for the (body weight [kg] +/- 0) mAs protocol, 1.3 for the (body weight [kg] - 10) mAs protocol, and 1.2 for the (body weight [kg] - 20) mAs protocol. Objective criteria based on noise measurements showed mean +/- standard deviation values of 5.7 +/- 0.8 Hounsfield units (HU) for the 120-mAs protocol. For the reduced-dose protocols, values were calculated as 7.6 +/- 1.2 HU (group + 10), 7.9 +/- 1.3 HU (group +/- 0), 8.7 +/- 1.2 HU (group - 10), and finally 9.1 +/- 1.3 HU (group - 20). The best correlation for an entire subgroup was achieved with the - 10 protocol (body weight [kg] - 10) mAs, with nearly constant noise related to body weight in all patients. CONCLUSIONS: By deriving mAs values from body weight estimation, an individually adapted protocol for chest CT can be recommended and easily employed in a clinical setting. With an adaptation of the tube current-time product based on the estimated body weight of the patient - 10 (body weight [kg] - 10 mAs), a well-balanced examination without significant loss of information, even in soft-tissue window settings, can be performed with this particular scanner. For this adapted mAs protocol, a mean reduction of radiation exposure of 45% was achievable, compared with the standard protocol. A maximum decrease per case down to 31 mAs was obtained, without relevant loss of image quality. Therefore, for other types of CT scanners, analogous protocols may be adapted.