Repeatability of transient elastography in children.

BACKGROUND: Poorly performing diagnostic tests can impact patient safety. Clinical investigations must have good precision and diagnostic accuracy before widespread use in clinical practice. Transient elastography (TE) measures liver stiffness, a surrogate marker of liver fibrosis in adults and children. Studies to evaluate its repeatability and reproducibility (precision) in children are limited. Our aim was to determine (i) the normal range of TE measurements and (ii) the repeatability and reproducibility of TE in healthy children. METHODS: TE was performed in 257 healthy children, of whom 235 (91%, mean age 11.7 years, standard deviation (SD) 2.51, 107 were males (45.5%)) had two valid TE measurements performed, at least 24 h apart, by two operators under similar circumstances. High-quality TE images were obtained for each examination. RESULTS: The normal range of TE was 2.88-6.52 kPa. The mean difference between paired measurements was 0.044 (SD 0.4). The 95% limits of agreement ranged from -0.8 to +0.76 kPa for repeat measurements. There was a difference of >1 kPa between measurements in 61/235 (25.9%) children. The lack of precision was similar across all age groups. CONCLUSIONS: This study demonstrates that TE does not have acceptable precision in healthy children, because random measurement variation results in the lack of agreement between paired measurements. IMPACT: The precision and diagnostic accuracy of a new technology must be determined before it is deployed in children in order to ensure that appropriate clinical decisions are made, and healthcare resources are not wasted. TE is widely used to diagnose liver disease in children without adequate evaluation of the precision (repeatability) of TE either in healthy children or children with liver disease. This study demonstrates that TE does not have adequate precision in children. This study was performed in accordance with methods previously published for children. Refinements to the test protocol, such as duration of fasting or probe size, will have to be evaluated for their impact on precision and accuracy before the test is deployed in research studies or clinical practice.

3T MRI of the knee with optimised isotropic 3D sequences: Accurate delineation of intra-articular pathology without prolonged acquisition times.

OBJECTIVES: To investigate optimised isotropic 3D turbo spin echo (TSE) and gradient echo (GRE)-based pulse sequences for visualisation of articular cartilage lesions within the knee joint. METHODS: Optimisation of experimental imaging sequences was completed using healthy volunteers (n=16) with a 3-Tesla (3T) MRI scanner. Imaging of patients with knee cartilage abnormalities (n=57) was then performed. Acquired sequences included 3D proton density-weighted (PDW) TSE (SPACE) with and without fat-suppression (FS), and T2*W GRE (TrueFISP) sequences, with acquisition times of 6:51, 6:32 and 5:35 min, respectively. RESULTS: One hundred sixty-one confirmed cartilage lesions were detected and categorised (Grade II n=90, Grade III n=71). The highest sensitivity and specificity for detecting cartilage lesions were obtained with TrueFISP with values of 84.7% and 92%, respectively. Cartilage SNR mean for PDW SPACE-FS was the highest at 72.2. TrueFISP attained the highest CNR means for joint fluid/cartilage (101.5) and joint fluid/ligament (156.5), and the lowest CNR for cartilage/meniscus (48.5). Significant differences were identified across the three sequences for all anatomical structures with respect to SNR and CNR findings (p-value <0.05). CONCLUSION: Isotropic TrueFISP at 3T, optimised for acquisition time, accurately detects cartilage defects, although it demonstrated the lowest contrast between cartilage and meniscus. KEY POINTS: • Cartilage is better visualised with 3D TrueFISP than 3D SPACE sequences. • 3D TrueFISP is a reliable sequence for detecting low- and high-grade cartilage defects. • 3D TrueFISP at 3T provides excellent contrast between cartilage and joint fluid.

Phosphate is not an absolute requirement for the inhibitory effects of cyclosporin A or cyclophilin D deletion on mitochondrial permeability transition.

CypD (cyclophilin D) has been established as a critical regulator of the MPT (mitochondrial permeability transition) pore, and pharmacological or genetic inhibition of CypD attenuates MPT in numerous systems. However, it has recently been suggested that the inhibitory effects of CypD inhibition only manifest when P(i) (inorganic phosphate) is present, and that inhibition is lost when P(i) is replaced by As(i) (inorganic arsenate) or V(i) (inorganic vanadate). To test this, liver mitochondria were isolated from wild-type and CypD-deficient (Ppif-/-) mice and then incubated in buffer containing P(i), As(i) or V(i). MPT was induced under both energized and de-energized conditions by the addition of Ca2+, and the resultant mitochondrial swelling was measured spectrophotometrically. For pharmacological inhibition of CypD, wild-type mitochondria were pre-incubated with CsA (cyclosporin A) before the addition of Ca2+. In energized and de-energized mitochondria, Ca2+ induced MPT regardless of the anion present, although the magnitude differed between P(i), As(i) and V(i). However, in all cases, pre-treatment with CsA significantly inhibited MPT. Moreover, these effects were independent of mouse strain, organ type and rodent species. Similarly, attenuation of Ca2+-induced MPT in the Ppif-/- mitochondria was still observed irrespective of whether P(i), As(i) or V(i) was present. We conclude that the pharmacological and genetic inhibition of CypD is still able to attenuate MPT even in the absence of P(i).

Evaluation of image quality of diffusion weighted readout segmentation of long variable echo-trains MR pulse sequence for lumbosacral nerve imaging at 3T.

Background: Limited magnetic resonance (MR) pulse sequences facilitate lumbosacral nerve imaging with acceptable image quality. This study aimed to evaluate the impact of parameter modification for Diffusion Weighted Image (DWI) using Readout Segmentation of Long Variable Echo-trains (RESOLVE) sequence with opportunities for improving the visibility of lumbosacral nerves and image quality. Methods: Following ethical approval and acquisition of informed consent, imaging of an MR phantom and twenty healthy volunteers (n=20) was prospectively performed with 3T MRI scanner. Acquired sequences included standard two-dimensional (2D) turbo spin echo sequences and readout-segmented echo-planar imaging (EPI) DWI-RESOLVE using three different b-values b-50, b-500 and b-800 s/mm2. Signal-to-noise ratio (SNR), apparent diffusion coefficient (ADC) and nerve size were measured. Two musculoskeletal radiologists evaluated anatomical structure visualisation and image quality. Quantitative and qualitative findings for healthy volunteers were investigated for differences using Wilcoxon signed-rank and Friedman tests, respectively. Inter and intra-observer agreement was determined with κ statistics. Results: Phantom images revealed higher SNR for images with low b-values with 206.1 (±10.9), 125.1 (±45.2) and 59.2 (±17.8) for DWI-RESOLVE images acquired at b50, b500 and b800, respectively. Comparable results were found for SNR, ADC and nerve size across normal right and left sided for healthy volunteer images. The SNR findings for b-50 images were higher than b-500 and b-800 images for healthy volunteer images. The qualitative findings ranked images acquired using b-50 and b-500 images significantly higher than corresponding b-800 images (P<0.05). Inter and intra-observer agreements for evaluation across all b-values ranged from 0.59 to 0.81 and 0.83 to 0.92, respectively. Conclusions: The modified DWI-RESOLVE images facilitated visualization of the normal lumbosacral nerves with acceptable image quality, which support the clinical applicability of this sequence.

Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death.

Opening of the MPT (mitochondrial permeability transition) pore is a critical event in mitochondrial-mediated cell death. However, with the exception of CypD (cyclophilin D), the exact molecular composition of the MPT pore remains uncertain. C1qbp (complement 1q-binding protein) has recently been hypothesized to be an essential component of the MPT pore complex. To investigate whether C1qbp indeed plays a critical role in MPT and cell death, we conducted both gain-of-function and loss-of-function experiments in MEFs (mouse embryonic fibroblasts). We first confirmed that C1qbp is a soluble protein that localizes to the mitochondrial matrix in mouse cells and tissues. Similarly, overexpression of C1qbp in MEFs using an adenovirus resulted in its exclusive localization to mitochondria. To our surprise, increased C1qbp protein levels actually suppressed H2O2-induced MPT and cell death. Antithetically, knockdown of endogenous C1qbp with siRNA (small interfering RNA) sensitized the MEFs to H2O2-induced MPT and cell death. Moreover, we found that C1qbp could directly bind to CypD. Therefore C1qbp appears to act as an endogenous inhibitor of the MPT pore, most likely through binding to CypD, and thus protects cells against oxidative stress.

Hypercholesterolemia increases mitochondrial oxidative stress and enhances the MPT response in the porcine myocardium: beneficial effects of chronic exercise.

Hypercholesterolemia has been suggested to have direct negative effects on myocardial function due to increased reactive oxygen species (ROS) generation and increased myocyte death. Mitochondrial permeability transition (MPT) is a significant mediator of cell death, which is enhanced by ROS generation and attenuated by exercise training. The purpose of this study was to investigate the effect of hypercholesterolemia on the MPT response of cardiac mitochondria. We tested the hypothesis that familial hypercholesterolemic (FH) pigs would have an enhanced MPT response and that exercise training could reverse this phenotype. MPT was assessed by mitochondrial swelling in response to 10-100 µM Ca(2+). FH pigs did show an increased MPT response to Ca(2+) that was associated with decreases in the expression of the putative MPT pore components mitochondrial phosphate carrier (PiC) and cyclophilin-D (CypD). FH also caused increased oxidative stress, depicted by increased protein nitrotyrosylation, as well as decreased levels of reduced GSH in cardiac mitochondria. Expression of the mitochondrial antioxidant enzymes manganese superoxide dismutase (MnSOD), thioredoxin-2 (Trx2), and peroxiredoxin-3 (Prx3) was greatly reduced in the FH pigs. In contrast, cytosolic catalase expression and activity were increased. However, chronic exercise training was able to normalize the MPT response in FH pigs, reduce mitochondrial oxidative stress, and return MnSOD, Trx2, Prx3, and catalase expression/activities to normal. We conclude that FH reduces mitochondrial antioxidants, increases mitochondrial oxidative stress, and enhances the MPT response in the porcine myocardium, and that exercise training can reverse these detrimental alterations.

Identifying lumbosacral plexus nerve root abnormalities in patients with sciatica using 3T readout-segmented echo-planar diffusion weighted MR neurography.

OBJECTIVES: To investigate the accuracy of Diffusion Weighted Imaging (DWI) using the Readout Segmentation of Long Variable Echo-trains (RESOLVE) sequence in detecting lumbosacral nerve abnormalities. METHODS: Following institutional ethics committee approval, patients with sciatica-type lower limb radicular symptoms (n = 110) were recruited and prospectively scanned using 3T MRI. Additional participants (n = 17) who underwent neurophysiological testing (EMG/NCV), were also prospectively studied. In addition to routine lumbar spine MRI, a DWI-RESOLVE sequence of the lumbosacral plexus was performed. Two radiologists, blinded to the side of patient symptoms, independently evaluated the MR images. The size and signal intensity changes of the nerves were evaluated using ordinal 4-point Likert-scales. Signal-to-noise ratio (SNR), apparent diffusion coefficient (ADC) and size were measured for affected and normal nerves. Inter-observer agreement was determined with kappa statistics; κ. RESULTS: In patients who did not undergo EMG/NCV testing (n = 110), the DWI-RESOLVE sequence detected lumbosacral nerve abnormalities that correlated with symptoms in 36.3% (40/110). This is a similar percentage to patients who underwent EMG/NCV testing, which was positive and correlated with symptoms in 41.2% (7/17). Inter-observer agreement for evaluation of lumbosacral nerve abnormalities was excellent and ranged from 0.87 to 0.94. SNR and nerve size measurements demonstrated statistically significant differences for the L5 and S1 nerves (p value < 0.05) for patients who did not undergo EMG/NCV testing. CONCLUSION: The DWI-RESOLVE sequence is a promising new method that may permit accurate detection and localization of lumbar nerve abnormalities in patients with sciatica.

A Comparison of MRI Radiographers' Knowledge in Saudi Arabia and the Republic of Ireland in Relation to Image Quality Management, for Abdomen and Pelvic MRI Examinations.

PURPOSE: The purpose of this article was to qualitatively compare current MRI radiographers' knowledge from Saudi Arabia and the Republic of Ireland in relation to MR image quality for abdominal and pelvic MRI examinations. METHODS AND MATERIALS: Semistructured interviews were designed to investigate the professional role of radiographers towards image quality management, personal development in MRI, and training in relation to image quality improvement. Public, private, military, and academic hospitals in the Western region of the Kingdom of Saudi Arabia participated, as did a range of public and private Irish centres. Clinical specialist radiographers (CSRs)/supervisors, and MR radiographers working in MR completed the interviews. These were recorded, coded, and transcribed. RESULTS: Sixty-one MR radiographers and CSRs/supervisors within 11 MRI departments in the Kingdom of Saudi Arabia and 11 MRI departments in the Republic of Ireland participated in this study. Three themes resulted by using a qualitative data analysis program called NVivo: (1) health care professional and the cultural attitudes with regards to the scope of professional roles, (2) factors affecting image quality, and (3) departmental policy. Participants' knowledge of image quality varied and challenges to achieving optimal quality levels were noted. Differences in clinical practice between countries were identified, as was the impact of clinical experience and levels of education. CONCLUSION: Differences in attitude and clinical practice between Saudi and Irish radiographers and CSRs/supervisors working in MRI departments were identified. There is a need for further training and subsequent assessment of professional skills, including developing postgraduate opportunities, particularly for Saudi radiographers, to support radiographers in the routine management of MR image quality.

Validation of the educational effectiveness of a mobile learning app to improve knowledge about MR image quality optimisation and artefact reduction.

AIM: The aim was to design an app-based eLearning tool to provide radiographers with information about the physical basis of MR artefacts and practical elimination or/and minimisation strategies to optimise image quality, and to evaluate the impact of a smartphone app on radiographers' knowledge. METHODS: The study used the comparison-experimental approach (pre- and post-test). Thirty-five MR radiographers independently reviewed a prepared series of MR images (n = 25). The participants were requested to identify image quality related errors, to specify error-correction strategies and to score how confident they were in their responses. Participants were then divided into experimental (n = 19) and control cohorts (n = 16). The app was provided to the experimental cohort for 3 months; after this period both cohorts re-reviewed the MR image datasets and repeated their identification of image quality errors. RESULTS: The results showed a statistically significant difference between control and experimental cohorts relative to participants' pre- to post-test knowledge level. For the experimental cohort, years of experience, qualification and type of hospital were not associated with radiographer knowledge level and confidence in recognising the presence of an image quality error, naming the error and specifying appropriate correction strategies (p > 0.05). CONCLUSION: The study identified the potential of the smartphone app as an effective educational tool to support MR radiographers' knowledge in recognising and characterising MR image quality errors. KEY POINTS: • A high level of knowledge to optimise MR image quality is crucial. • Ongoing education in image quality optimisation is required. • The potential role of app as an effective educational tool is identified.

The mitochondrial protein C1qbp promotes cell proliferation, migration and resistance to cell death.

Complement 1q-Binding Protein (C1qbp) is a mitochondrial protein reported to be upregulated in cancer. However, whether C1qbp plays a tumor suppressive or tumorigenic role in the progression of cancer is controversial. Moreover, the exact effects of C1qbp on cell proliferation, migration, and death/survival have not been definitely proven. To this end, we comprehensively examined the effects of C1qbp on mitochondrial-dependent cell death, proliferation, and migration in both normal and breast cancer cells using genetic gain- and loss-of-function approaches. In normal fibroblasts, overexpression of C1qbp protected the cells against staurosporine-induce apoptosis, increased proliferation, decreased cellular ATP, and increased cell migration in a wound-healing assay. In contrast, the opposite effects were observed in fibroblasts depleted of C1qbp by RNA interference. C1qbp expression was found to be markedly elevated in 4 different human breast cancer cell lines as well as in ductal and adenocarcinoma tumors from breast cancer patients. Stable knockdown of C1qbp by shRNA in the aggressive MDA-MB-231 breast cancer cell line greatly reduced cell proliferation, increased ATP levels, and decreased cell migration compared to control shRNA-transfected cells. Moreover, C1qbp knockdown elicited a significant increase in doxorubicin-induced apoptosis in the MDA-MB-231 cells. Finally, C1qbp upregulation was not restricted to breast cancer cells and tumors, as levels of C1qbp were also found to be significantly elevated in both human lung and colon cancer cell lines and carcinomas. Together, these results establish a pro-tumor, rather than anti-tumor, role for C1qbp, and indicate that C1qbp could serve as a molecular target for cancer therapeutics.

Increased Acquisition Speed Settings can Significantly Decrease Patient Dose while Maintaining Imaging Quality during Direct Chest Radiography.

BACKGROUND: Chest imaging using direct acquisition technology has reduced dose in comparison to the traditional film screen techniques. This work investigates the potential for further dose reduction through the use of increased exposure class. AIMS: To compare 400 and 800 speed acquisition on the GE Revolution XQ/i direct radiography system for posteroanterior chest radiography, 30 patients were examined from a population of males and females ages 18-65 years with a body mass index (BMI) of 17-28 kg/m2. Effective doses were recorded for each patient, and image quality was evaluated using anatomical image quality criteria. RESULTS: Images acquired at 400 speed were found to have 25% higher image quality than those at 800 speed (P ≤ .001), with an effective dose 55% higher (P ≤ .009). Radiographs of patients with an average BMI of 17-24.9 kg/m2 taken at 800 speed were found to be diagnostically acceptable. CONCLUSIONS: Radiographs produced at 800 speed on a direct radiography system are acceptable for patients below 25 kg/m2 delivering 55% less effective dose (P ≤ .009) than 800 speed. Patients with a BMI above 25 kg/m2 require 400 speed acquisition.