Influence of fractional anisotropy thresholds on diffusion tensor imaging tractography of the periprostatic neurovascular bundle and selected pelvic tissues: do visualized tracts really represent nerves?

Background Diffusion tensor imaging (DTI) tractography has recently been shown to successfully visualize periprostatic tracts allegedly representing the neurovascular bundle. Purpose To examine the impact of different fractional anisotropy (FA) thresholds on the results of DTI tractography in the male pelvis as well as to evaluate the resulting specificity for nerve tracts. Material and Methods Ten healthy male volunteers were examined at 3 Tesla. DTI tractography was performed based on seed points placed circularly around the prostate, in the rectoprostatic angle, the peripheral zone of the prostate, the sciatic nerve, and in addition the urinary bladder using FA thresholds of 0.20, 0.05, and 0.01. DTI tract number and DTI tract length measured with different FA thresholds were compared. ANOVA with repeated measures was used for statistics. Results DTI tract number and tract length were significantly dependent on FA thresholds. While a FA threshold of 0.20 visualized the typical distribution of DTI tracts in the sciatic nerve, a FA threshold of ≤0.05 was necessary to yield results visually mimicking the distribution of nerve tracts in the NVB. However, with such low FA thresholds even in the filled urinary bladder DTI tracts could be visualized. With FA thresholds of 0.20, the number and length of periprostatic DTI tracts did not differ from those measured within the prostate. Conclusion DTI tractography can be used to visualize DTI tracts periprostatically. However, one may doubt that these DTI tracts represent nerve tracts and that the periprostatic neurovascular bundle can be evaluated in a meaningful way with the current methods available.

Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure.

OBJECTIVE: To examine the value of additional transrectal ultrasonography (TRUS)-guided random biopsy (RB) in patients with negative magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB) and to identify possible reasons for TB failure. PATIENTS AND METHODS: We conducted a subgroup analysis of 61 men with prostate cancer (PCa) detected by 10-core RB but with a negative TB, from a cohort of 408 men with suspicious multiparametric magnetic resonance imaging (mpMRI) between January 2012 and January 2015. A consensus re-reading of mpMRI results (using Prostate Imaging Reporting and Data System [PI-RADS] versions 1 and 2) for each suspicious lesion was performed, with the image reader blinded to the biopsy results, followed by an unblinded anatomical correlation of the lesion on mpMRI to the biopsy result. The potential reasons for TB failure were estimated for each lesion. We defined clinically significant PCa according to the Epstein criteria and stratified patients into risk groups according to the European Association of Urology guidelines. RESULTS: Our analysis showed that RB detected significant PCa in 64% of patients (39/61) and intermediate-/high-risk PCa in 57% of patients (35/61). The initial mpMRI reading identified 90 suspicious lesions in the cohort. Blinded consensus re-reading of the mpMRI led to PI-RADS score downgrading of 45 lesions (50%) and upgrading of 13 lesions (14%); thus, negative TB could be explained by falsely high initial PI-RADS scores for 32 lesions (34%) and sampling of the target lesion by RB in the corresponding anatomical site for 36 out of 90 lesions (40%) in 35 of 61 patients (57%). Sampling of the target lesion by RB was most likely for lesions with PI-RADS scores of 4/5 and Gleason scores (GS) of ≥7. A total of 70 PCa lesions (67% with GS 6) in 44 patients (72%) were sampled from prostatic sites with no abnormalities on mpMRI. CONCLUSION: In cases of TB failure, RB still detected a high rate of significant PCa. The main reason for a negative TB was a TB error, compensated for by positive sampling of the target lesion by the additional RB, and the second reason for TB failure was a falsely high initial PI-RADS score. The challenges that arise for both MRI diagnostics and prostate lesion sampling are evident in our data and support the integration of RB into the TB workflow.

The detection of significant prostate cancer is correlated with the Prostate Imaging Reporting and Data System (PI-RADS) in MRI/transrectal ultrasound fusion biopsy.

PURPOSE: To evaluate the performance of real-time MRI/ultrasound (MRI/US) fusion-guided targeted biopsy (TB) in men with primary and repeat biopsies and correlate the prostate cancer detection rate (CDR) with the PI-RADS score. METHODS: Analysis included 408 consecutive men with primary and prior negative biopsies who underwent TB and 10-core random biopsy (RB) between January 2012 and January 2015. TB was performed with a real-time MRI/US fusion platform with sensor-based registration. Clinically significant PCa was defined as Gleason score (GS) ≥ 7 or GS 6 with maximal cancer core length ≥ 4 mm for TB and according to Epstein criteria for RB. RESULTS: The overall CDR was 56 % (227/408). The CDR for primary biopsy was 74 % (60/81) and 57 % (67/117), 49 % (62/126), 45 % (38/84) for patients with 1, 2 and ≥ 3 prior negative biopsies. CDRs correlated with PI-RADS 2/3/4/5 were 16 % (5/32), 26 % (29/113), 62 % (94/152) and 89 % (99/111), respectively. The rates of significant tumors in relation to PI-RADS 2/3/4/5 were 60 % (3/5), 66 % (19/29), 74 % (70/94), 95 % (94/99). In 139 (61 %) cases with radical prostatectomy (RP), the rates of ≥ pT3 tumors in correlation with PI-RADS 4 and 5 were 20 % (11/56) and 49 % (32/65). PI-RADS constituted the strongest predictor of significant PCa detection (p < 0.007). CONCLUSIONS: Real-time MRI/US fusion-guided TB combined with RB improved PCa detection in patients with primary and repeat biopsies. The CDR was strongly correlated with a rising PI-RADS score, values of 4 and 5 increasing the detection of clinically significant tumors and leading to a higher histological stage after RP.

The value of ADC, T2 signal intensity, and a combination of both parameters to assess Gleason score and primary Gleason grades in patients with known prostate cancer.

BACKGROUND: The ability to non-invasively analyze tumor aggressiveness is an important predictor for individual treatment stratification and patient outcome in prostate cancer (PCA). PURPOSE: To evaluate: (i) whether apparent diffusion coefficient (ADC), the T2 signal intensity (SI), and a combination of both parameters allow for an improved discrimination of Gleason Score (GS) ≥7 (intermediate and high risk) and GS <7 (low risk) in PCA; and (ii) whether ADC may distinguish between 3 + 4 and 4 + 3 PCA (primary Gleason grades [pGG]). MATERIAL AND METHODS: Prostatectomy specimens of 66 patients (mean age, 63 ± 5.6 years; 104 PCA foci) with a preceding multiparametric 1.5 T endorectal coil magnetic resonance imaging (MRI) were included. ADC (b values = 0, 100, 400, 800 s/mm(2)), standardized T2 (T2s), and the ADC/T2s ratio were tested for correlation with GS applying multivariate analysis. ADC cutoff values were calculated for prediction of GS and pGG, and logarithm of the odds (LOGIT) was used to express the probability for GS and pGG. Diagnostic accuracy was assessed by ROC analysis. RESULTS: We found an almost linear negative relationship of ADC for GS ≥7 (P = 0.002). The effect of ADC for GS ≥7 (adjusted odds ratio = 0.995) was almost identical for peripheral and transition zone PCA (P = 0.013 and P < 0.001, respectively). ADC showed an AUC of 78.9% for discrimination between GS <7 and GS ≥7. An ADC cutoff of <1.005 × 10(-3 )mm(2)/s indicated a GS ≥7 (90.5% sensitivity, 62.5% specificity). Within the group of GS = 7 PCA, an ADC > 0.762 × 10(-3 )mm(2)/s indicated a pGG of 3 (AUC = 69.6%). CONCLUSION: T2s and the ADC/T2s ratio do not provide additional information regarding prediction of GS. ADC values have a good discriminatory power to distinguish tumors with GS ≥7 from GS <7 and to predict pGG in GS = 7 PCA.

Low Dose Computed Tomography for 3D Planning of Total Hip Arthroplasty: Evaluation of Radiation Exposure and Image Quality.

OBJECTIVE: The aim of the study was to compare radiation exposure and image quality between dedicated computed tomography (CT) protocols for preoperative total hip arthroplasty (THA) planning. METHODS: Three protocols with automated tube current modulation using 64-slice (n = 177) and 128-slice CT scanners without (n = 129) and with automated tube voltage preselection (n = 84) were compared. RESULTS: All 390 CTs were of sufficient quality for THA planning. Mean DLP was 235.0 mGy*cm (effective dose 2.8 mSv). Lowest radiation exposure (2.5 mSv) was seen with automated voltage preselection and the algorithm's selection was 100 kV (90.5% of patients) and 120 kV. Lowest image noise was seen in the highest dose group (3.1 mSv, 128-slice CT fixed tube voltage). A significant difference in cortical bone radiodensity was seen between 100 kV and 120 kV (P < 0.0001). CONCLUSIONS: Preoperative pelvic CT for THA planning is possible with very low radiation dose and reliable quality. Automated voltage preselection further decreases the effective dose by 18.2%.

High-pitch dual-source CT coronary angiography with low volumes of contrast medium.

OBJECTIVES: To assess the effect of lower volumes of contrast medium (CM) on image quality in high-pitch dual-source computed tomography coronary angiography (CTCA). METHODS: One-hundred consecutive patients (body weight 65-85 kg, stable heart rate ≤65 bpm, cardiac index ≥2.5 L/min/m(2)) referred for CTCA were prospectively enrolled. Patients were randomly assigned to one of five groups of different CM volumes (G30, 30 mL; G40, 40 mL; G50, 50 mL; G60, 60 mL; G70, 70 mL; flow rate 5 mL/s each, iodine content 370 mg/mL). Attenuation within the proximal and distal coronary artery segments was analysed. RESULTS: Mean attenuation for men and women ranged from 345.0 and 399.1 HU in G30 to 478.2 and 571.8 HU in G70. Mean attenuation values were higher in groups with higher CM volumes (P < 0.0001) and higher in women than in men (P < 0.0001). The proportions of segments with attenuation of at least 300 HU in G30, G40, G50, G60 and G70 were 89 %, 95 %, 98 %, 98 % and 99 %. CM volume of 30 mL in women and 40 mL in men proved to be sufficient to guarantee attenuation of at least 300 HU. CONCLUSIONS: In selected patients high-pitch dual-source CTCA can be performed with CM volumes of 40 mL in men or 30 mL in women. KEY POINTS: • High-pitch dual-source coronary angiography is feasible with low contrast media volumes. • Traditional injection rules still apply: higher volumes result in higher enhancement. • The patient's gender is a co-factor determining the level of contrast enhancement. • Volumes can be reduced down to 30-40 mL in selected patients.

Myosin IXb variants and their pivotal role in maintaining the intestinal barrier: a study in Crohn's disease.

BACKGROUND: Myosin IXb (MYO9B) is involved in the regulation of epithelial barrier function. We hypothesized that MYO9B variants are associated with increased intestinal permeability measured in patients with Crohn's disease (CD), where barrier dysfunction is crucially involved in disease development. METHODS: We sequenced MYO9B and genotyped five MYO9B variants (rs1545620, rs1457092, rs2279003, rs2305764 and rs2279002) and correlated these data to measurement of intestinal permeability in German CD patients (n = 122) obtained by standard oral sugar test using the lactulose/mannitol ratio after measurement of urinary excretion. We furthermore studied MYO9B variants in three European cohorts with inflammatory bowel disease (IBD) and healthy controls : Germany (CD = 264; ulcerative colitis = 143 [UC]; HC = 372); Hungary (CD = 147; UC = 117; HC = 195), the Netherlands (CD = 157; HC = 219). RESULTS: We found an association for four studied MYO9B variants to an increased intestinal permeability in CD patients (rs1545620, p = 0.010; rs1457092, p = 0.024; rs2279003, p = 0.003; rs2305764, p = 0.015). Furthermore, we observed significantly higher absolute values of intestinal permeability for individuals carrying risk alleles within MYO9B. Looking for an overall disease association, only the rs2305764 variant was associated with CD in the Dutch cohort (p = 0.004), but not in the German or Hungarian cohort. No association to UC or a distinct phenotype in both CD and UC patients was observed for all studied MYO9B variants. CONCLUSION: Our data suggest a link between MYO9B variants to an increased intestinal permeability in CD patients. This supports the influence of Myosin IXb on the integrity of the epithelial barrier. The role of MYO9B variants in the overall susceptibility to IBD, however, remains to be elucidated.

Macrocyclic contrast agents for magnetic resonance imaging of chronic myocardial infarction: intraindividual comparison of gadobutrol and gadoterate meglumine.

OBJECTIVES: To compare 0.15 mmol/kg gadobutrol for late gadolinium enhancement (LGE) imaging of chronic myocardial infarction with a relaxivity-adjusted dose of gadoterate meglumine (Gd-DOTA). METHODS: Seventeen patients with suspected chronic myocardial infarction underwent LGE imaging at 1.5 T, acquiring an inversion-recovery-prepared gradient echo sequence 15 min after contrast agent administration. Each patient underwent LGE imaging twice, once after administration of 0.15 mmol/kg gadobutrol (r1 = 5.2 l mmol(-1) s(-1)) and after 0.22 mmol/kg Gd-DOTA (r1 = 3.6 l mmol(-1) s(-1)). Two readers independently determined infarct size and contrast-to-noise ratios of infarcted myocardium to remote myocardium (CNR(remote)) and to the left ventricular lumen (CNR(lumen)). RESULTS: LGE was present in 14 patients. Infarct sizes determined after administration of gadobutrol [23.4 ml; 95 % CI (14.4; 32.5)] and Gd-DOTA [22.1 ml; 95 % CI (13.0; 31.1)] were not statistically different (P = 0.22). The CNR(remote) of LGE in infarcted myocardium on gadobutrol- and Gd-DOTA-enhanced images was 44.1 [95 % CI (31.0; 57.1)] and 45.2 [95 % CI (32.2; 58.3)], respectively (P = 0.73). CNR(lumen) was significantly higher on gadobutrol-enhanced LGE images [12.7; 95 % CI (2.5; 23.0) versus 6.8; 95 % CI (-3.5; 17.0); P = 0.02]. CONCLUSION: At relaxivity-adjusted doses, gadobutrol and Gd-DOTA yielded similar infarct sizes with superior contrast between infarcted myocardium and left ventricular lumen on gadobutrol-enhanced images.

Single beat 3D echocardiography for the assessment of right ventricular dimension and function after endurance exercise: Intraindividual comparison with magnetic resonance imaging.

BACKGROUND: Our study compares new single beat 3D echocardiography (sb3DE) to cardiovascular magnetic resonance imaging (CMR) for the measurement of right ventricular (RV) dimension and function immediately after a 30 km run. This is to validate sb3DE against the "gold standard" CMR and to bring new insights into acute changes of RV dimension and function after endurance exercise. METHODS: 21 non-elite male marathon runners were examined by sb3DE (Siemens ACUSON SC2000, matrix transducer 4Z1c, volume rates 10-29/s), CMR (Siemens Magnetom Avanto, 1,5 Tesla) and blood tests before and immediately after each athlete ran 30 km. The runners were not allowed to rehydrate after the race. The order of sb3DE and CMR examination was randomized. RESULTS: Sb3DE for the acquisition of RV dimension and function was feasible in all subjects. The decrease in mean body weight and the significant increase in hematocrit indicated dehydration. RV dimensions measured by CMR were consistently larger than measured by sb3DE.Neither sb3DE nor CMR showed a significant difference in the RV ejection fraction before and after exercise. CMR demonstrated a significant decrease in RV dimensions. Measured by sb3DE, this decrease of RV volumes was not significant. CONCLUSION: First, both methods agree well in the acquisition of systolic RV function. The dimensions of the RV measured by CMR are larger than measured by sb3DE. After exercise, the RV volumes decrease significantly when measured by CMR compared to baseline.Second, endurance exercise seems not to induce acute RV dysfunction in athletes without rehydration.

Low-dose triple-rule-out using 320-row-detector volume MDCT--less contrast medium and lower radiation exposure.

OBJECTIVES: To investigate image quality of triple-rule-out (TRO) computed tomography (CT) using a 320-row-detector CT system with substantially reduced contrast medium volume at 100 kV. METHODS: Forty-six consecutive patients with noncritical, acute chest pain underwent 320-row-detector CT using a two-step TRO protocol consisting of a non-spiral, non-gated chest CT acquisition (150 mA) followed by a non-spiral, electrocardiography-gated cardiac acquisition (200-500 mA based on body mass index (BMI)). Data were acquired using a biphasic injection protocol with a total iodinated contrast medium volume of 60 ml (370 mg/ml). Vessel attenuation and effective doses were recorded. Image quality was scored independently by two readers. RESULTS: Mean attenuation was 584 ± 114 Hounsfield units (HU) in the ascending aorta, 335 ± 63HU in the aortic arch, 658 ± 136HU in the pulmonary trunk, and 521 ± 97HU and 549 ± 102HU in the right and left coronary artery, respectively. In all but one patient, attenuation and image quality allowed accurate visualization of the pulmonary arteries, thoracic aorta, and coronary arteries in a single examination. Ninety-six percent of all coronary artery segments were rated diagnostic. Radiation exposure ranged between 2.0 and 3.3 mSv. CONCLUSION: Using 320-row-detector CT the investigated low-dose TRO protocol resulted in excellent opacification and image quality with substantial reduction of contrast medium volume compared to recently published TRO protocols.

Cardiac magnetic resonance imaging in dilated cardiomyopathy in adults--towards identification of myocardial inflammation.

OBJECTIVE: To assess active myocardial inflammation by cardiovascular magnetic resonance (CMR) and endomyocardial biopsy (EMB) amongst adult patients with dilated cardiomyopathy (DCM). METHODS: We evaluated 23 adults with chronic DCM, who had successfully undergone both CMR and EMB within 3.5 ± 2.6 days. EMB was considered the gold standard. CMR assessment of myocardial inflammation used the following parameters as recommended by the recently published "Lake Louise Criteria": global myocardial oedema, global relative enhancement (RE), and late gadolinium enhancement (LGE). According to "Lake Louise Criteria", myocardial inflammation was diagnosed if two or more of the three above-mentioned parameters were positive. RESULTS: Myocardial inflammation was confirmed by immunohistology in 12 patients (52.2%). Sensitivity, specificity, and diagnostic accuracy of CMR to detect immunohistologically confirmed myocardial inflammation were 75.0%, 72.7%, and 73.9%, respectively. Sensitivity, specificity, and diagnostic accuracy of the individual CMR parameters to detect myocardial inflammation were as follows: global myocardial oedema, 91.7%, 81.8%, and 87.0%, respectively; global RE, 58.3%, 63.6%, and 60.9%, respectively; LGE, 58.3%, 45.4%, and 52.2%, respectively. CONCLUSION: Global myocardial oedema was identified as a promising CMR parameter for assessment of myocardial inflammation in patients with DCM. In these patients, global myocardial oedema yielded superior diagnostic performance compared to "Lake Louise Criteria".

Assessment of mitral valve stenosis by helical MDCT: comparison with transthoracic doppler echocardiography and cardiac catheterization.

OBJECTIVE: We evaluated the precision of helical MDCT for the quantification of mitral valve stenosis (MVS) compared with transthoracic echocardiography (TTE) and cardiac catheterization. MATERIALS AND METHODS: A total of 28 patients with MVS of differing severity underwent an ECG-gated contrast-enhanced MDCT scan. The mitral valve area (MVA) was determined planimetrically by MDCT and was compared with Doppler TTE using the pressure half-time method and with cardiac catheterization using the Gorlin formula. RESULTS: Planimetry of the MVA with MDCT was feasible in all cases. The MVA on MDCT (1.88 ± 0.76 cm(2)) was significantly larger than that seen with TTE (1.74 ± 0.75 cm(2); p = 0.039) or cardiac catheterization (1.72 ± 0.67 cm(2); p = 0.037). The correlation between MDCT and TTE (r = 0.90; p < 0.001; limits of agreement, ± 0.65 cm(2)) and that between MDCT and cardiac catheterization (r = 0.86; p < 0.001; limits of agreement, ± 0.76 cm(2)) were good and similar to the correlation between TTE and cardiac catheterization (r = 0.88; p < 0.001; limits of agreement, ± 0.71 cm(2)). The best cutoff level for detecting moderate-to-severe stenosis at MDCT was an MVA of 1.70 cm(2), resulting in a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 73%, 88%, 82%, 80%, and 83%, respectively, with two false-positive and three false-negative results. CONCLUSION: The MVA planimetrically determined by MDCT is systematically larger than those calculated by Doppler TTE and cardiac catheterization. However, because of a good correlation between methods and adjustment for the systematic bias, MDCT may allow reliable quantification of MVS and effectual discrimination among severity grades, although discrepancies between methods remain in individual cases.

Comparison of non-gated vs. electrocardiogram-gated 64-detector-row computed tomography for integrated electroanatomic mapping in patients undergoing pulmonary vein isolation.

AIMS: To compare non-gated vs. electrocardiogram (ECG)-gated 64-detector-row computed tomography (MDCT) of the left atrium (LA) for integrated electroanatomic mapping (EAM) in patients with paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Twenty-nine consecutive patients with paroxysmal AF underwent MDCT prior to pulmonary vein isolation (PVI). All patients were in sinus rhythm both during CT imaging and PVI. Multi-detector-row computed tomography was performed in 15 patients without ECG-gating (non-gated MDCT) and in 14 patients with retrospective ECG-gating (ECG-gated MDCT). Image quality of LA reconstructions from MDCT was rated on a five-point scale (from 1 = excellent to 5 = segmentation failed). Registration error between LA geometry obtained from EAM and MDCT was calculated as the mean distance between EAM points and MDCT surface. In all patients, LA was successfully segmented from MDCT data. The segmentation process took 2:31 +/- 0:54 min for non-gated MDCT and 2:36 +/- 0:47 min for ECG-gated MDCT (P = 0.8). Image quality scores of LA reconstructions from non-gated and ECG-gated MDCT were 1.3 +/- 0.6 and 1.4 +/- 0.7, respectively (P = 0.76). There was no significant difference in the registration error between non-gated and ECG-gated MDCT (1.8 +/- 0.2 vs. 1.9 +/- 0.3 mm, respectively; P = 0.6). The radiation dose of non-gated MDCT was significantly lower compared with ECG-gated MDCT (4.6 +/- 1.4 vs. 13.4 +/- 3.6 mSv, respectively; P < 0.001). CONCLUSION: Non-gated MDCT depicts LA with appropriate image quality for integrated EAM, while exposing patients to substantially lower radiation dose compared with ECG-gated MDCT.

Survivin minigene DNA vaccination is effective against neuroblastoma.

The inhibitor of apoptosis protein survivin is highly expressed in neuroblastoma (NB) and survivin-specific T cells were identified in Stage 4 patients. Therefore, we generated a novel survivin minigene DNA vaccine (pUS-high) encoding exclusively for survivin-derived peptides with superior MHC class I (H2-K(k)) binding affinities and tested its efficacy to suppress tumor growth and metastases in a syngeneic NB mouse model. Vaccination was performed by oral gavage of attenuated Salmonella typhimurium SL7207 carrying pUS-high. Mice receiving the pUS-high in the prophylactic setting presented a 48-52% reduction in s.c. tumor volume, weight and liver metastasis level in contrast to empty vector controls. This response was as effective as a survivin full-length vaccine and was associated with an increased target cell lysis, increased presence of CD8(+) T-cells at the primary tumor site and enhanced production of proinflammatory cytokines by systemic CD8(+) T cells. Furthermore, depletion of CD8(+) but not CD4(+) T-cells completely abrogated the pUS-high mediated primary tumor growth suppression, demonstrating a CD8(+) T-cell mediated effect. Therapeutic vaccination with pUS-high led to complete NB eradication in over 50% of immunized mice and surviving mice showed an over 80% reduction in primary tumor growth upon rechallenge in contrast to controls. In summary, survivin-based DNA vaccination is effective against NB and the rational minigene design provides a promising approach to circumvent potentially hazardous effects of using full length antiapoptotic genes as DNA vaccines.

Cthrc1 is a novel inhibitor of transforming growth factor-beta signaling and neointimal lesion formation.

We identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene expressed in the adventitia and neointima on arterial injury and found that it functionally increases cell migration while reducing collagen deposition. To address the in vivo role of Cthrc1, we generated transgenic mouse lines that constitutively overexpress Cthrc1. An intercross of 2 transgenic lines produced offspring with brittle bones caused by a reduction in collagenous bone matrix. Hemizygous Cthrc1 transgenic mice developed normally but neointimal lesion formation and adventitial collagen deposition in response to carotid artery ligation were significantly reduced compared with wild-type littermates. In 75% of Cthrc1 transgenic mice, cartilaginous metaplasia of medial smooth muscle cells was observed as assessed by Alcian blue staining and expression of the chondrocyte marker collagen type II. Transforming growth factor-beta signaling was reduced in smooth muscle cells of Cthrc1 transgenic arteries, as demonstrated by reduced phospho-Smad2/3 immunoreactivity, whereas Smad signaling related to bone morphogenetic proteins was unaffected. Similarly, primary smooth muscle cells and PAC1 smooth muscle cells overexpressing Cthrc1 had reduced levels of phospho-Smad2/3 as well as procollagen. Furthermore, Cthrc1 inhibited transforming growth factor-beta-sensitive reporter constructs in smooth muscle but not endothelial cells. These data indicate that Cthrc1 is a cell-type-specific inhibitor of transforming growth factor-beta, which in turn impacts collagen type I and III deposition, neointimal formation, and dedifferentiation of smooth muscle cells.

Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1).

We recently identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene induced in adventitial fibroblasts after arterial injury. Cthrc1 is a 30 kDa secreted protein that has the ability to inhibit collagen matrix synthesis. Cthrc1 is also glycosylated and retains a signal sequence consistent with the presence of Cthrc1 in the extracellular space. In injured arteries and skin wounds, we have found Cthrc1 expression to be associated with myofibroblasts and sites of collagen matrix deposition. Furthermore, we demonstrated that Cthrc1 inhibits collagen matrix deposition in vitro. Using in situ hybridization and immunohistochemistry, we characterized the expression domains of Cthrc1 during murine embryonic development and in postnatal tissues. In mouse embryos, Cthrc1 was expressed in the visceral endoderm, notochord, neural tube, developing kidney, and heart. Abundant expression of Cthrc1 was observed in the developing skeleton, i.e., in cartilage primordia, in growth plate cartilage with exclusion of the hypertrophic zone, in the bone matrix and periostium. Bones from adults showed expression of Cthrc1 only in the bone matrix and periostium while the articular cartilage lacked expression. Cthrc1 is typically expressed at epithelial-mesenchymal interfaces that include the epidermis and dermis, basal corneal epithelium, airway epithelium, esophagus epithelium, choroid plexus epithelium, and meninges. In the adult kidney, collecting ducts and distal tubuli expressed Cthrc1. Collectively, the sites of Cthrc1 expression overlap considerably with those reported for TGF-beta family members and interstitial collagens. The present study provides useful information towards the understanding of potential Cthrc1 functions.

Individual selection of X-ray tube settings in computed tomography coronary angiography: Reliability of an automated software algorithm to maintain constant image quality.

OBJECTIVES: To evaluate a software tool that claims to maintain a constant contrast-to-noise ratio (CNR) in high-pitch dual-source computed tomography coronary angiography (CTCA) by automatically selecting both X-ray tube voltage and current. METHODS: A total of 302 patients (171 males; age 61±12years; body weight 82±17kg, body mass index 27.3±4.6kg/cm(2)) underwent CTCA with a topogram-based, automatic selection of both tube voltage and current using dedicated software with quality reference values of 100kV and 250mAs/rotation (i.e., standard values for an average adult weighing 75kg) and an injected iodine load of 222mg/kg. RESULTS: The average radiation dose was estimated to be 1.02±0.64mSv. All data sets had adequate contrast enhancement. Average CNR in the aortic root, left ventricle, and left and right coronary artery was 15.7±4.5, 8.3±2.9, 16.1±4.3 and 15.3±3.9 respectively. Individual CNR values were independent of patients' body size and radiation dose. However, individual CNR values may vary considerably between subjects as reflected by interquartile ranges of 12.6-18.6, 6.2-9.9, 12.8-18.9 and 12.5-17.9 respectively. Moreover, average CNR values were significantly lower in males than females (15.1±4.1 vs. 16.6±11.7 and 7.9±2.7 vs. 8.9±3.0, 15.5±3.9 vs. 16.9±4.6 and 14.7±3.6 vs. 16.0±4.1 respectively). CONCLUSION: A topogram-based automatic selection of X-ray tube settings in CTCA provides diagnostic image quality independent of patients' body size. Nevertheless, considerable variation of individual CNR values between patients and significant differences of CNR values between males and females occur which questions the reliability of this approach.

A new method of calculating the rotation angle in pediatric forearm fractures using direct radiographs.

BACKGROUND: The aim of this study was to measure the rotational angle defect between fracture ends in paediatric forearm diaphyseal fractures on radiographs. METHODS: Evaluations were performed on 78 paediatric patients who presented at the emergency department with a diaphyseal forearm fracture during 2013-2014. Thirty-two patients who underwent conservative treatment and had < 10° of angulation and translation of not more than half the bone diameter after application of a plaster cast were included in the study. A rotational formula was used with diameter values to determine changes. The degree of rotation of both ends of the fracture line and the forearm rotational defect of the fracture line were calculated. FINDINGS: Fractures included an isolated radius in 16 cases, an isolated ulna in four cases, and both bones in 12 cases. The mean lateral angular (LAT-θ) value was 26.13 ± 5.93° on the proximal fracture end, and the distal mean LAT-θ was 30.29 ± 6.24° (p = 0.037).The mean proximal anteroposterior angular (AP-θ) value was 26.83 ± 5.75°, and the distal mean AP-θ was 30.58 ± 7.27° (p = 0.008). A significant correlation was detected between the AP-Δ and LAT-Δ measurements (p = 0.883). INTERPRETATION: The rotational defect was mathematically calculated directly from radiographs using a rotational measurement formula.

T2- and diffusion-weighted magnetic resonance imaging at 3T for the detection of prostate cancer with and without endorectal coil: An intraindividual comparison of image quality and diagnostic performance.

OBJECTIVES: To intraindividually compare image quality and diagnostic performance of multiparametric MRI (mpMRI) at 3T for the detection of prostate cancer (PCa) using a pelvic phased-array coil (PAC) and a combined endorectal and pelvic phased-array coil (ERC-PAC). METHODS: Forty-five patients were prospectively included and received mpMRI of the prostate using a PAC and an ERC-PAC during one imaging session. Two radiologists evaluated image quality and the most suspicious lesion according to the PI-RADS scoring system. Results of MRI-TRUS-fusion biopsy of the prostate served as reference standard. Patient comfort and acceptance were assessed using a standardized questionnaire. RESULTS: Overall image quality for T2WI was rated significantly better with an ERC-PAC compared to a PAC (p=0.0038). The weighted kappa for PI-RADS scores for T2WI and DWI with a PAC and an ERC-PAC was 0.70 and 0.73, respectively. For a PI-RADS sum score including T2WI and DWI the area under the curve with a PAC and an ERC-PAC were 0.95-0.99 and 0.93-0.97, respectively (p=0.1395). CONCLUSION: For T2WI and DWI performed at 3T index PCa lesion identification and evaluation did not differ significantly with both coil setups. Patients preferred MRI without an ERC. Therefore, the use of an ERC may be omitted in a prostate cancer detection setting.

Added Value of Multiparametric Ultrasonography in Magnetic Resonance Imaging and Ultrasonography Fusion-guided Biopsy of the Prostate in Patients With Suspicion for Prostate Cancer.

OBJECTIVE: To analyze whether magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided biopsy detects more and clinical significant prostate cancer (PCa) in comparison to conventional transrectal US-guided prostate biopsy (PBX) and to investigate if multiparametric (mp) US during MRI-US fusion can further characterize mpMRI-suspected lesions according to the prostate MRI reporting and data system (PI-RADS). METHODS: From January 2012 to January 2014, 169 patients with a median of 2 negative conventional PBX and/or initially or consistently elevated prostate-specific antigen levels were prospectively included and underwent 3 T mpMRI. Real-time MRI-US fusion scan was used to biopsy the mpMRI-targeted lesions (n = 316). Scanning by mpUS, including B-mode, power Doppler, strain elastography, and contrast-enhanced US was performed to further characterize those lesions and to score by US modalities resulting in an mpUS score. Afterward, a conventional 10-core PBX was performed. PCa detection based on the results of targeted and conventional PBX was estimated. Performances of single US modalities were analyzed. The mpUS score was also investigated for PCa and PI-RADS score prediction. RESULTS: Among 169 patients, 71 PCa (42%) were detected. From these 71 cases, clinically significant PCa (Gleason score ≥7) were detected exclusively by MRI-US fusion in 31 from 46 cases (67.4%). The highest sensitivity was observed in contrast-enhanced US (85%) and elastography (80%). The mpUS score predicts PCa and PI-RADS score with an overall accuracy of 86% and 80%, respectively. CONCLUSION: MRI-US fusion-guided PBX detects more clinically significant PCa compared with conventional TRUS. The mpUS score correlates with PI-RADS in PCa prediction.