It's a thin line: development and validation of Dixon MRI-based semi-quantitative assessment of stress-related bone marrow edema in the wrists of young gymnasts and non-gymnasts.

PURPOSE: To assess reliability and clinical utility of evaluating stress-related metaphyseal water distribution using a semi-quantitative Dixon MRI-based method for early diagnosis of physeal stress injuries in adolescent gymnasts. METHODS: Twenty-four gymnasts with clinically suspected overuse injury of the distal radial physis, 18 asymptomatic gymnasts, and 24 non-gymnast controls aged 12 ± 1.5 years prospectively underwent hand radiographs and 3T MRI of the wrist including coronal T1-weighted and T2-weighted Dixon sequences. Two raters measured metaphyseal water signal fraction in 13 radial and ulnar regions of interest (ROI). Inter- and intrarater reliability, interslice (between 3 middle radial slices), and inter-ROI (between 3 ROIs on same level) reliability were assessed using intraclass correlation coefficients (ICC). Water signal fractions and their within-person ratios in distal versus most proximal ROIs were compared between groups using one-way analysis of variance. RESULTS: Inter- and intrarater ICCs were 0.79-0.99 and 0.94-1.0 for T1-weighted, and 0.88-1.0 and 0.88-1.0 for T2-weighted Dixon. Interslice and inter-ROI ICCs were 0.55-0.94 and 0.95-0.97 for T1-weighted, and 0.70-0.96 and 0.96-0.97 for T2-weighted Dixon. Metaphyseal water signal fraction in symptomatic gymnasts was higher in six distal ROIs compared with asymptomatic gymnasts and in nine ROIs compared with non-gymnasts (p < 0.05). Metaphyseal water score (ratio of distal versus most proximal ROIs) was 1.61 in symptomatic gymnasts and 1.35 in asymptomatic gymnasts on T2-weighted Dixon (p < 0.05). CONCLUSION: Semi-quantitative Dixon MRI-based water signal fraction assessment has good to excellent reproducibility and shows increased metaphyseal water scores in symptomatic gymnasts compared with asymptomatic gymnastic peers. KEY POINTS: • The proposed Dixon MRI-based semi-quantitative method for assessment of metaphyseal bone marrow water content is reliable, with off-the-shelf availability and short scan times. • The metaphyseal water score allows comparisons between gymnasts using a within-person reference area for unaffected metaphyseal bone. • As metaphyseal water score was increased in symptomatic gymnasts compared with asymptomatic gymnasts, this semi-quantitative method can potentially be used as an indicator of bone marrow edema in the early diagnosis of gymnastic physeal stress injury.

TrimetaziDine as a Performance-enhancING drug in heart failure with preserved ejection fraction (DoPING-HFpEF): rationale and design of a placebo-controlled cross-over intervention study.

BACKGROUND: Currently, no specific treatment exists for heart failure with preserved ejection fraction (HFpEF). Left ventricular (LV) relaxation during diastole is a highly energy-demanding process, while energy homeostasis is known to be compromised in HFpEF. We hypothesise that trimetazidine - a fatty acid ß­oxidation inhibitor - improves LV diastolic function in HFpEF, by altering myocardial substrate use and improving the myocardial energy status. OBJECTIVES: To assess whether trimetazidine improves LV diastolic function by improving myocardial energy metabolism in HFpEF. METHODS: The DoPING-HFpEF trial is a randomised, double-blind, placebo-controlled cross-over intervention trial comparing the efficacy of trimetazidine and placebo in 25 patients with stable HFpEF. The main inclusion criteria are: New York Heart Association functional class II to IV, LV ejection fraction ≥50%, and evidence of LV diastolic dysfunction. Patients are treated with one 20-mg trimetazidine tablet or placebo thrice daily (twice daily in the case of moderate renal dysfunction) for two periods of 3 months separated by a 2-week washout period. The primary endpoint is the change in pulmonary capillary wedge pressure during different intensities of exercise measured by right heart catheterisation. Our key secondary endpoint is the myocardial phosphocreatine (PCr)/ATP ratio measured by phosphorus-31 magnetic resonance spectroscopy and its relation to the primary endpoint. Exploratory endpoints are 6­min walk distance, N-terminal pro-brain natriuretic peptide levels, and quality of life. CONCLUSION: The DoPING-HFpEF is a phase-II trial that evaluates the effect of trimetazidine, a metabolic modulator, on diastolic function and myocardial energy status in HFpEF. [EU Clinical Trial Register: 2018-002170-52; NTR registration: NL7830].

Transcatheter aortic valve replacement alters ascending aortic blood flow and wall shear stress patterns: A 4D flow MRI comparison with age-matched, elderly controls.

BACKGROUND: With the implementation of transcatheter aortic valve replacement (TAVR) in lower-risk patients, evaluation of blood flow characteristics and the effect of TAVR on aortic dilatation becomes of considerable interest. We employed 4D flow MRI in the ascending aorta of patients after TAVR to assess wall shear stress (WSS) and compare blood flow patterns with surgical aortic valve replacement (SAVR) and age- and gender-matched controls. METHODS: Fourteen post-TAVR patients and ten age- and gender-matched controls underwent kt-PCA accelerated 4D flow MRI of the thoracic aorta at 3.0 Tesla. Velocity and wall shear stress was compared between the two groups. In addition, aortic flow eccentricity and displacement was assessed and compared between TAVR patients, controls and 14 SAVR patients recruited as part of an earlier study. RESULTS: Compared to controls, abnormally elevated WSS was present in 30±10% of the ascending aortic wall in TAVR patients. Increased WSS was present along the posterior mid-ascending aorta and the anterior distal-ascending aorta in all TAVR patients. TAVR results in eccentric and displaced flow in the mid- and distal-ascending aorta, whereas blood flow displacement in SAVR patients occurs only in the distal-ascending aorta. CONCLUSION: This study shows that TAVR results in increased blood flow velocity and WSS in the ascending aorta compared to age- and gender-matched elderly controls. This finding warrants longitudinal assessment of aortic dilatation after TAVR in the era of potential TAVR in lower-risk patients. Additionally, TAVR results in altered blood flow eccentricity and displacement in the mid- and distal-ascending aorta, whereas SAVR only results in altered blood flow eccentricity and displacement in the distal-ascending aorta. KEY POINTS: • TAVR results in increased blood flow velocity and WSS in the ascending aorta. • Longitudinal assessment of aortic dilatation after TAVR is warranted in the era of potential TAVR in lower-risk patients. • Both TAVR and SAVR result in altered blood flow patterns in the ascending aorta when compared to age-matched controls.

Meal timing effects on insulin sensitivity and intrahepatic triglycerides during weight loss.

BACKGROUND: Several human and rodent studies suggest that in addition to the amount of energy consumed, timing of food intake contributes to body weight regulation. Consuming most energy in the morning has favorable effects on weight loss and weight maintenance. Whether this also affects glucose metabolism and liver fat independently from weight loss is unknown. OBJECTIVE: We hypothesized that during weight loss, consuming most energy in the morning improves insulin sensitivity and reduces hepatic fat content more than consuming most energy in the evening. METHODS: Twenty-three obese insulin resistant men (age 59.9±7.9 years, body mass index 34.4±3.8 kg m-2) followed a 4-week hypocaloric diet intervention with either 50% of daily energy consumed in the morning (BF group) or evening (D group). Insulin sensitivity, measured with a two-step hyperinsulinemic euglycemic clamp using a glucose tracer, intrahepatic triglycerides (IHTG), measured using magnetic resonance spectroscopy, and resting energy expenditure (REE) were assessed before and after the diet intervention. RESULTS: Meal macronutrient composition and weight loss (6.5±1.5% vs 6.2±1.9%, respectively, P=0.70) did not differ between the BF and D groups. Endogenous glucose production (P⩽0.001), hepatic and peripheral insulin sensitivity (P=0.002; P=0.001, respectively) as well as IHTG content (P⩽0.001) all significantly improved with weight loss, but were not different between the BF and D groups. In addition, both groups decreased REE and respiratory quotient equally. CONCLUSIONS: During weight loss, consuming most energy in the morning instead of the evening does not have additional beneficial effects on insulin sensitivity and IHTG content. These results do not support weight independent effects of meal timing on glucose metabolism and IHTG in hypocaloric conditions in obese men.

Breast magnetic resonance elastography: a review of clinical work and future perspectives.

This review on magnetic resonance elastography (MRE) of the breast provides an overview of available literature and describes current developments in the field of breast MRE, including new transducer technology for data acquisition and multi-frequency-derived power-law behaviour of tissue. Moreover, we discuss the future potential of breast MRE, which goes beyond its original application as an additional tool in differentiating benign from malignant breast lesions. These areas of ongoing and future research include MRE for pre-operative tumour delineation, staging, monitoring and predicting response to treatment, as well as prediction of the metastatic potential of primary tumours.

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study.

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .

Cerebral dopamine deficiency, plasma monoamine alterations and neurocognitive deficits in adults with phenylketonuria.

BACKGROUND: Phenylketonuria (PKU), a genetic metabolic disorder that is characterized by the inability to convert phenylalanine to tyrosine, leads to severe intellectual disability and other cerebral complications if left untreated. Dietary treatment, initiated soon after birth, prevents most brain-related complications. A leading hypothesis postulates that a shortage of brain monoamines may be associated with neurocognitive deficits that are observable even in early-treated PKU. However, there is a paucity of evidence as yet for this hypothesis. METHODS: We therefore assessed in vivo striatal dopamine D2/3 receptor (D2/3R) availability and plasma monoamine metabolite levels together with measures of impulsivity and executive functioning in 18 adults with PKU and average intellect (31.2 ± 7.4 years, nine females), most of whom were early and continuously treated. Comparison data from 12 healthy controls that did not differ in gender and age were available. RESULTS: Mean D2/3R availability was significantly higher (13%; p = 0.032) in the PKU group (n = 15) than in the controls, which may reflect reduced synaptic brain dopamine levels in PKU. The PKU group had lower plasma levels of homovanillic acid (p < 0.001) and 3-methoxy-4-hydroxy-phenylglycol (p < 0.0001), the predominant metabolites of dopamine and norepinephrine, respectively. Self-reported impulsivity levels were significantly higher in the PKU group compared with healthy controls (p = 0.033). Within the PKU group, D2/3R availability showed a positive correlation with both impulsivity (r = 0.72, p = 0.003) and the error rate during a cognitive flexibility task (r = 0.59, p = 0.020). CONCLUSIONS: These findings provide further support for the hypothesis that executive functioning deficits in treated adult PKU may be associated with cerebral dopamine deficiency.

Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies.

Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: a head-to-head comparison with ¹5O H2O positron emission tomography.

Measurements of the cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide useful information about cerebrovascular condition and regional metabolism. Pseudo-continuous arterial spin labeling (pCASL) is a promising non-invasive MRI technique to quantitatively measure the CBF, whereas additional hypercapnic pCASL measurements are currently showing great promise to quantitatively assess the CVR. However, the introduction of pCASL at a larger scale awaits further evaluation of the exact accuracy and precision compared to the gold standard. (15)O H2O positron emission tomography (PET) is currently regarded as the most accurate and precise method to quantitatively measure both CBF and CVR, though it is one of the more invasive methods as well. In this study we therefore assessed the accuracy and precision of quantitative pCASL-based CBF and CVR measurements by performing a head-to-head comparison with (15)O H2O PET, based on quantitative CBF measurements during baseline and hypercapnia. We demonstrate that pCASL CBF imaging is accurate during both baseline and hypercapnia with respect to (15)O H2O PET with a comparable precision. These results pave the way for quantitative usage of pCASL MRI in both clinical and research settings.

Evaluation of an imaging biomarker, Dixon quantitative chemical shift imaging, in Gaucher disease: lessons learned.

Gaucher disease (GD) is the first lysosomal storage disorder for which specific therapy became available. The infiltration of bone marrow by storage cells plays an important part in the pathophysiology of skeletal complications and can be quantified by measurements of bone marrow fat fraction (Ff). Ff measurements by Dixon quantitative chemical shift imaging (QCSI) are standard for the follow-up care of GD patients at the Academic Medical Center. Several criteria should be met in order for these measurements to qualify as an imaging biomarker. These include: 1) The presence of the imaging biomarker is closely coupled or linked to the presence of the target disease or condition; 2) The detection and/or quantitative measurement of the biomarker is accurate, reproducible, and feasible over time, and; 3) The changes measured over time in the imaging biomarker are closely coupled, or linked, to the success or failure of the therapeutic effect and the true end point for the medical therapy being evaluated. This review assesses the use of Ff measurements by QCSI as a biomarker for GD in light of these criteria. In addition potential pitfalls are discussed including: degenerative disc disease; vertebral collapse and infection; haematological malignancies; focal fatty deposits; age; menopause; phase and repositioning errors, and; fat surrounding the basivertebral vein.QCSI measurements of Ff can be used as an imaging biomarker for GD taking these pitfalls into account. It is one of the first biomarkers, in particular imaging biomarkers, for GD that has been systematically evaluated and could be a valuable tool in clinical trials comparing different treatments or dosing regimens.

Mapping the hemodynamic response in human subjects to a dopaminergic challenge with dextroamphetamine using ASL-based pharmacological MRI.

Pharmacological magnetic resonance imaging (phMRI) maps the neurovascular response to a pharmacological challenge and is increasingly used to assess neurotransmitter systems. Here we investigated the hemodynamic response to a dopaminergic (DAergic) challenge with dextroamphetamine (dAMPH) in humans using arterial spin labeling (ASL) based phMRI. Twelve healthy male subjects aged 21.0years (±1.5) were included. We used a pseudo-continuous ASL sequence (40min) to quantify cerebral blood flow (CBF) and started dAMPH infusion (0.3mg/kg) after 10min. On another day, we measured baseline dopamine D2/3 receptor availability with [(123)I]IBZM single photon emission computed tomography (SPECT). Baseline measures on mood and impulsivity and subjective behavioral responses to dAMPH were obtained. CBF response was corrected for cardiovascular effects using an occipital cortex mask for internal reference. Corrected CBF (sCBF) was analyzed using ROI-based and voxel-based analysis, in addition to independent component analysis (ICA). CBF data was correlated to D2/3 receptor availability and behavioral measures. Subjects reported experiencing euphoria following dAMPH administration. In the striatum sCBF significantly increased, as demonstrated by all three analysis methods. Voxel-based analysis and ICA also showed increased sCBF in the thalamus, anterior cingulate and cerebellum. Decreased sCBF was observed in several cortical areas, the posterior cingulated and paracingulate cortex. Apart from one ICA component, no correlations were found with sCBF changes and D2/3 receptor availability and behavioral measures. Our observations are in line with literature and provide further evidence that ASL-based phMRI with dAMPH is a promising technique to assess DAergic function in human subjects.

Quantification and visualization of flow in the Circle of Willis: time-resolved three-dimensional phase contrast MRI at 7 T compared with 3 T.

The assessment of both geometry and hemodynamics of the intracranial arteries has important diagnostic value in internal carotid occlusion, sickle cell disease, and aneurysm development. Provided that signal to noise ratio (SNR) and resolution are high, these factors can be measured with time-resolved three-dimensional phase contrast MRI. However, within a given scan time duration, an increase in resolution causes a decrease in SNR and vice versa, hampering flow quantification and visualization. To study the benefits of higher SNR at 7 T, three-dimensional phase contrast MRI in the Circle of Willis was performed at 3 T and 7 T in five volunteers. Results showed that the SNR at 7 T was roughly 2.6 times higher than at 3 T. Therefore, segmentation of small vessels such as the anterior and posterior communicating arteries succeeded more frequently at 7 T. Direction of flow and smoothness of streamlines in the anterior and posterior communicating arteries were more pronounced at 7 T. Mean velocity magnitude values in the vessels of the Circle of Willis were higher at 3 T due to noise compared to 7 T. Likewise, areas of the vessels were lower at 3 T. In conclusion, the gain in SNR at 7 T compared to 3 T allows for improved flow visualization and quantification in intracranial arteries.

Feasibility of ASL-based phMRI with a single dose of oral citalopram for repeated assessment of serotonin function.

Assessment of cerebral serotonin (5-HT) function with arterial spin labeling (ASL)-based pharmacological magnetic resonance imaging (phMRI) could be a highly useful tool in clinical psychiatric research. The goal of this study was to verify the reliability of ASL-based phMRI after an oral challenge of a selective serotonin reuptake inhibitor (SSRI) in repeated assessment of cerebral 5-HT function. In a placebo-controlled, within-subject crossover study we investigated the effect of a single oral dose of citalopram on brain cerebral blood flow (CBF) using a pulsed ASL sequence (PASL) in twelve female healthy volunteers. The within-session repeatability of the PASL signal was good for all regions tested (wsCV<15%). Both ROI- and voxel-based analyses revealed small but significant effects of a citalopram challenge on CBF values in 5-HT rich brain regions, among which the frontal gyrus and thalamus. These effects could however not be replicated between sessions, most probably due to the small effect size of the oral citalopram challenge on cerebral blood flow. We therefore conclude that the test-retest reliability of PASL phMRI with an oral citalopram challenge is low, limiting the technique's sensitivity to time-dependent changes and consequently its use as a (clinical) research tool.

Lasting effects of chronic fluoxetine treatment on the late developing rat brain: age-dependent changes in the serotonergic neurotransmitter system assessed by pharmacological MRI.

RATIONALE: With the growing prevalence of psychotropic drug prescriptions among children and adolescents, the need for studies on lasting effects of drug exposure on the developing brain rises. Fluoxetine is the only selective serotonin reuptake inhibitor (SSRI) officially registered to treat major depressive disorder in children. Although various (pre)clinical studies have assessed the (long-term) effects of fluoxetine exposure in the perinatal period and in adulthood, limited data is available on its effects on the developing brain later in life, i.e. during adolescence. OBJECTIVE: The present study aimed at investigating the effects of age following chronic SSRI treatment on the central serotonin (5-HT) system. To this end, pharmacological MRI (phMRI) was performed in chronic fluoxetine-treated (5 mg/kg, oral gavage for 3 weeks) juvenile (PND25) and adult rats (PND65) after a 1-week washout period, using an acute fluoxetine challenge (5 mg/kg, i.v.) to trigger the 5-HT system. RESULTS: We observed a diminished brain response to the acute challenge in adult treated animals when compared to control animals, whereas this response was increased in juvenile treated rats. As a result, a significant age by treatment interaction effect was seen in several (subcortical) 5-HT related brain regions. CONCLUSION: An opposite effect of chronic fluoxetine treatment was seen in the developing brain compared to that in matured brain, as assessed non-invasively using phMRI. These findings most likely reflect neuronal imprinting effects of juvenile SSRI treatment and may underlie emotional disturbances seen in animals and children treated with this drug. Also, our findings suggest that phMRI might be ideally suited to study this important issue in the pediatric population.

Optimization of alternating TR-SSFP for fat-suppression in abdominal images at 3T.

Magnetic resonance imaging is widely used in the work-up and monitoring of patients with Crohn's disease. Balanced steady-state free precession sequences are an important part of the imaging protocol and until now primarily 1.5T scanners have been used in daily clinical practice. This is largely because running balanced steady-state free precession sequences in 3T magnets has technical problems related to increased B(0) inhomogeneity and specific absorption rate (SAR) deposition. A modified form of alternating repetition time steady-state free precession sequence is presented to acquire 3D-isotropic abdominal images with fat-suppression at 3T within a breath-hold. The modifications include an adjusted radiofrequency pulse shape, suitable phase-cycling scheme and TR(1)/TR(2) ratio. Results show that the proposed sequence is successful in obtaining high contrast 3D-isotropic abdominal images within a breath-hold. Furthermore, the proposed methodology is easy to implement in a clinical setting and does not require any postprocessing steps.

Complex flow patterns in a real-size intracranial aneurysm phantom: phase contrast MRI compared with particle image velocimetry and computational fluid dynamics.

The aim of this study was to validate the flow patterns measured by high-resolution, time-resolved, three-dimensional phase contrast MRI in a real-size intracranial aneurysm phantom. Retrospectively gated three-dimensional phase contrast MRI was performed in an intracranial aneurysm phantom at a resolution of 0.2 × 0.2 × 0.3 mm(3) in a solenoid rat coil. Both steady and pulsatile flows were applied. The phase contrast MRI measurements were compared with particle image velocimetry measurements and computational fluid dynamics simulations. A quantitative comparison was performed by calculating the differences between the magnitude of the velocity vectors and angles between the velocity vectors in corresponding voxels. Qualitative analysis of the results was executed by visual inspection and comparison of the flow patterns. The root-mean-square errors of the velocity magnitude in the comparison between phase contrast MRI and computational fluid dynamics were 5% and 4% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 16° and 14° for the steady and pulsatile measurements, respectively. In the phase contrast MRI and particle image velocimetry comparison, the root-mean-square errors were 12% and 10% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 19° and 15° for the steady and pulsatile measurements, respectively. Good agreement was found in the qualitative comparison of flow patterns between the phase contrast MRI measurements and both particle image velocimetry measurements and computational fluid dynamics simulations. High-resolution, time-resolved, three-dimensional phase contrast MRI can accurately measure complex flow patterns in an intracranial aneurysm phantom.

Evaluation of the female pelvic floor in pelvic organ prolapse using 3.0-Tesla diffusion tensor imaging and fibre tractography.

OBJECTIVES: To prospectively explore the clinical application of diffusion tensor imaging (DTI) and fibre tractography in evaluating the pelvic floor. METHODS: Ten patients with pelvic organ prolapse, ten with pelvic floor symptoms and ten asymptomatic women were included. A two-dimensional (2D) spin-echo (SE) echo-planar imaging (EPI) sequence of the pelvic floor was acquired. Offline fibre tractography and morphological analysis of pelvic magnetic resonance imaging (MRI) were performed. Inter-rater agreement for quality assessment of fibre tracking results was evaluated using weighted kappa (κ). From agreed tracking results, eigen values (λ1, λ2, λ3), mean diffusivity (MD) and fractional anisotropy (FA) were calculated. MD and FA values were compared using ANOVA. Inter-rater reliability of DTI parameters was interpreted using the intra-class correlation coefficient (ICC). RESULTS: Substantial inter-rater agreement was found (κ = 0.71 [95% CI 0.63-0.78]). Four anatomical structures were reliably identified. Substantial inter-rater agreement was found for MD and FA (ICC 0.60-0.91). No significant differences between groups were observed for anal sphincter, perineal body and puboperineal muscle. A significant difference in FA was found for internal obturator muscle between the prolapse group and the asymptomatic group (0.27 ± 0.05 vs 0.22 ± 0.03; P = 0.015). CONCLUSION: DTI with fibre tractography permits identification of part of the clinically relevant pelvic structures. Overall, no significant differences in DTI parameters were found between groups. KEY POINTS: Diffusion tensor MRI offers new insights into female pelvic floor problems. DTI allows 3D visualisation and quantification of female pelvic floor anatomy. DTI parameters from pelvic floor structures can be reliably determined. No significant differences in DTI parameters between groups with/without prolapse.

Dynamic magnetic resonance imaging to quantify pelvic organ prolapse: reliability of assessment and correlation with clinical findings and pelvic floor symptoms.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the interobserver agreement of magnetic resonance imaging (MRI)-based staging of pelvic organ prolapse (POP) and to quantify associations between MRI-based POP staging, findings at pelvic examination, and pelvic floor symptoms. METHODS: This was a cross-sectional study of ten symptomatic POP patients, ten symptomatic patients without POP, and ten nulliparous asymptomatic women. Three different observers performed MRI-based POP staging using the pubococcygeal line (PCL), midpubic line (MPL), perineal line, and H line as references. RESULTS: The interobserver agreement of MRI-based staging of the anterior and middle compartment was good to excellent. In symptomatic women without prolapse, MRI-based and pelvic-examination-based POP staging were poorly correlated. In none of the women were MRI-based POP Quantification (POP-Q) staging and pelvic floor symptoms strongly associated. CONCLUSION: The interobserver agreement of MRI-based POP staging is excellent, but the added clinical value of such staging is questionable due to poor association with clinical findings and pelvic floor symptoms.

The relationship between quantitative magnetic resonance imaging of the ankle plantar flexors, muscle function during walking and maximal strength in people with neuromuscular diseases.

BACKGROUND: Progression of plantar flexor weakness in neuromuscular diseases is usually monitored by muscle strength measurements, although they poorly relate to muscle function during walking. Pathophysiological changes such as intramuscular adipose tissue affect dynamic muscle function independent from isometric strength. Diffusion tensor imaging and T2 imaging are quantitative MRI measures reflecting muscular pathophysiological changes, and are therefore potential biomarkers to monitor plantar flexor functioning during walking in people with neuromuscular diseases. METHODS: In fourteen individuals with plantar flexor weakness diffusion tensor imaging and T2 scans of the plantar flexors were obtained, and the diffusion indices fractional anisotropy and mean diffusivity calculated. With a dynamometer, maximal isometric plantar flexor strength was measured. 3D gait analysis was used to assess maximal ankle moment and power during walking. FINDINGS: Fractional anisotropy, mean diffusivity and T2 relaxation time all moderately correlated with maximal plantar flexor strength (r > 0.512). Fractional anisotropy and mean diffusivity were not related with ankle moment or power (r < 0.288). T2 relaxation time was strongly related to ankle moment (r = -0.789) and ankle power (r = -0.798), and moderately related to maximal plantar flexor strength (r < 0.600). INTERPRETATION: In conclusion, T2 relaxation time, indicative of multiple pathophysiological changes, was strongly related to plantar flexor function during walking, while fractional anisotropy and mean diffusivity, indicative of fiber size, only related to maximal plantar flexor strength. This indicates that these measures may be suitable to monitor muscle function and gain insights into the pathophysiological changes underlying a poor plantar flexor functioning during gait in people with neuromuscular diseases.

Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia.

AIMS/HYPOTHESIS: Hepatic steatosis is strongly associated with hepatic and whole-body insulin resistance. It has proved difficult to determine whether hepatic steatosis itself is a direct cause of insulin resistance. In patients with familial hypobetalipoproteinaemia (FHBL), hepatic steatosis is a direct consequence of impaired hepatic VLDL excretion, independently of metabolic derangements. Thus, patients with FHBL provide a unique opportunity to investigate the relation between increased liver fat and insulin sensitivity. METHODS: We included seven male participants with FHBL and seven healthy matched controls. Intrahepatic triacylglycerol content and intramyocellular lipid content were measured using localised proton magnetic resonance spectroscopy (¹H-MRS). A two-step hyperinsulinaemic-euglycaemic clamp, using stable isotopes, was assessed to determine hepatic and peripheral insulin sensitivity. RESULTS: ¹H-MRS showed moderate to severe hepatic steatosis in patients with FHBL. Basal endogenous glucose production (EGP) and glucose levels did not differ between the two groups, whereas insulin levels tended to be higher in patients compared with controls. Insulin-mediated suppression of EGP during lower dose insulin infusion and insulin-mediated peripheral glucose uptake during higher dose insulin infusion were comparable between FHBL participants and controls. Baseline fatty acids and lipolysis (glycerol turnover) at baseline and during the clamp did not differ between groups. CONCLUSIONS/INTERPRETATION: In spite of moderate to severe hepatic steatosis, people with FHBL do not display a reduction in hepatic or peripheral insulin sensitivity compared with healthy matched controls. These results indicate that hepatic steatosis per se is not a causal factor leading to insulin resistance. TRIAL REGISTRATION: ISRCTN35161775.