Evaluation of Acute Supplementation With the Ketone Ester (R)-3-Hydroxybutyl-(R)-3-Hydroxybutyrate (deltaG) in Healthy Volunteers by Cardiac and Skeletal Muscle 31P Magnetic Resonance Spectroscopy.

In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (31P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23-70 years for cardiac 31P-MRS, and 16 aged 60-75 years for skeletal muscle 31P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle 31P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG®, was administered after the baseline scan. Administration was timed so that post-intervention 31P-MRS would take place 30 min after deltaG® ingestion. The deltaG® ketone drink was well-tolerated by all participants. In participants who provided blood samples, post-intervention blood glucose, lactate and non-esterified fatty acid concentrations decreased significantly (-28.8%, p ≪ 0.001; -28.2%, p = 0.02; and -49.1%, p ≪ 0.001, respectively), while levels of the ketone body D-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol/L after 30 min (p ≪ 0.001). There were no significant changes in cardiac PCr/ATP or skeletal muscle metabolic parameters between baseline and post-intervention. Acute ketone supplementation caused mild ketosis in blood, with drops in glucose, lactate, and free fatty acids; however, such changes were not associated with changes in 31P-MRS measures in the heart or in skeletal muscle. Future work may focus on the effect of longer-term ketone supplementation on tissue energetics in groups with compromised mitochondrial function.

A novel method for measuring bowel motility and velocity with dynamic magnetic resonance imaging in two and three dimensions.

Increasingly, dynamic magnetic resonance imaging (MRI) has potential as a noninvasive and accessible tool for diagnosing and monitoring gastrointestinal motility in healthy and diseased bowel. However, current MRI methods of measuring bowel motility have limitations: requiring bowel preparation or long acquisition times; providing mainly surrogate measures of motion; and estimating bowel-wall movement in just two dimensions. In this proof-of-concept study we apply a method that provides a quantitative measure of motion within the bowel, in both two and three dimensions, using existing, vendor-implemented MRI pulse sequences with minimal bowel preparation. This method uses a minimised cost function to fit linear vectors in the spatial and temporal domains. It is sensitised to the spatial scale of the bowel and aims to address issues relating to the low signal-to-noise in high-temporal resolution dynamic MRI scans, previously compensated for by performing thick-slice (10-mm) two-dimensional (2D) coronal scans. We applied both 2D and three-dimensional (3D) scanning protocols in two healthy volunteers. For 2D scanning, analysis yielded bi-modal velocity peaks, with a mean antegrade motion of 5.5 mm/s and an additional peak at ~9 mm/s corresponding to longitudinal peristalsis, as supported by intraoperative data from the literature. Furthermore, 3D scans indicated a mean forward motion of 4.7 mm/s, and degrees of antegrade and retrograde motion were also established. These measures show promise for the noninvasive assessment of bowel motility, and have the potential to be tuned to particular regions of interest and behaviours within the bowel.

Measuring liver fat fraction with complex-based chemical shift MRI: the effect of simplified sampling protocols on accuracy.

BACKGROUND: The assessment of liver percentage fat fraction (%FF) using proton density fat fraction sequences is becoming increasingly accessible. Previous studies have tended to use multiple small ROIs that focus on Couinaud segments. In an effort to simplify day-to-day analysis, this study assesses the impact of using larger, elliptical ROIs focused on a single hepatic lobe. Additionally, we assess the impact of sampling fewer transhepatic slices when measuring %FF. METHODS: Retrospective analysis of prospectively obtained images from 34 volunteers using an IDEAL IQ sequence. Two observers independently measured %FF using three different protocols: freehand whole-liver ROI (fh-ROI), elliptical-ROI on the right lobe (rt-ROI) and elliptical-ROI on the left lobe (lt-ROI). RESULTS: Inter-observer reliability for all measurements techniques was 'excellent' (Spearman's rank correlation coefficients 0.81-0.98). There was a significant difference (Paired Wilcoxon Test: p < 0.001) between the median %FF obtained using fh-ROI when compared to the rt-ROI method, the maximum mean difference between the two techniques was 2.79% (95% CI). For all sampling methods a Kruskall-Wallis analysis demonstrated no significant difference in mean %FF when the number of slices sampled was reduced from 11 to 1. The mean coefficient of variance increased when more slices were sampled (3 slices = 0.1, 11 slices = 0.17, p < 0.001). CONCLUSION: Simplified ROIs focused on one hepatic lobe provide %FF measurements that are unlikely to be sufficiently accurate for use in clinical practice. Freehand whole-liver ROIs should be used in preference. A single freehand ROI measurement taken at the level of the hepatic hilum yields a %FF that is representative of the mean whole liver % FF. Multiple slices are needed to measure heterogeneity.

The diagnostic accuracy of high b-value diffusion- and T2-weighted imaging for the detection of prostate cancer: a meta-analysis.

PURPOSE: This study aims to investigate the role of diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) in combination for the detection of prostate cancer, specifically assessing the role of high b-values (> 1000 s/mm2), with a systematic review and meta-analysis of the existing published data. METHODS: The electronic databases MEDLINE, EMBASE, and OpenSIGLE were searched between inception and September 1, 2017. Eligible studies were those that reported the sensitivity and specificity of DWI and T2WI for the diagnosis of prostate cancer by visual assessment using a histopathologic reference standard. The QUADAS-2 critical appraisal tool was used to assess the quality of included studies. A meta-analysis with pooling of sensitivity, specificity, likelihood, and diagnostic odds ratios was undertaken, and a summary receiver-operating characteristics (sROC) curve was constructed. Predetermined subgroup analysis was also performed. RESULTS: Thirty-three studies were included in the final analysis, evaluating 2949 patients. The pooled sensitivity and specificity were 0.69 (95% CI 0.68-0.69) and 0.84 (95% CI 0.83-0.85), respectively, and the sROC AUC was 0.84 (95% CI 0.81-0.87). Subgroup analysis showed significantly better sensitivity with high b-values (> 1000 s/mm2). There was high statistical heterogeneity between studies. CONCLUSION: The diagnostic accuracy of combined DWI and T2WI is good with high b-values (> 1000 s/mm2) seeming to improve overall sensitivity while maintaining specificity. However, further large-scale studies specifically looking at b-value choice are required before a categorical recommendation can be made.

Parameter Estimation Error Dependency on the Acquisition Protocol in Diffusion Kurtosis Imaging.

Mono-exponential kurtosis model is routinely fitted on diffusion weighted, magnetic resonance imaging data to describe non-Gaussian diffusion. Here, the purpose was to optimize acquisitions for this model to minimize the errors in estimating diffusion coefficient and kurtosis. Similar to a previous study, covariance matrix calculations were used, and coefficients of variation in estimating each parameter of this model were calculated. The acquisition parameter, b values, varied in discrete grids to find the optimum ones that minimize the coefficient of variation in estimating the two non-Gaussian parameters. Also, the effect of variation of the target values on the optimized values was investigated. Additionally, the results were benchmarked with Monte Carlo noise simulations. Simple correlations were found between the optimized b values and target values of diffusion and kurtosis. For small target values of the two parameters, there is higher chance of having significant errors; this is caused by maximum b value limits imposed by the scanner than the mathematical bounds. The results here, cover a wide range of parameters D and K so that they could be used in many directionally averaged diffusion weighted cases such as head and neck, prostate, etc.

Test-retest reliability of rapid whole body and compartmental fat volume quantification on a widebore 3T MR system in normal-weight, overweight, and obese subjects.

PURPOSE: To measure the test-retest reliability of rapid (<15 min) whole body and visceral fat volume quantification in normal and obese subjects on a widebore 3T MR system and compare it with conventional manual segmentation. MATERIALS AND METHODS: Thirty participants (body mass index [BMI] 20.1-48.6 kg/m2 ) underwent two whole-body magnetic resonance imaging (MRI) examinations on a widebore 3T machine using a 2-point Dixon technique. Phase sensitive reconstruction and intensity inhomogeneity correction produced quantitative datasets of total adipose tissue (TAT), abdominal subcutaneous adipose tissue (ASAT), and visceral adipose tissue (VAT). The quantification was performed automatically using nonrigid atlas-based segmentation and compared with manual segmentation (SliceOmatic). RESULTS: The mean TAT was 31.74 L with a coefficient of variation (CV) of 0.79% and a coefficient of repeatability (CR) of 0.49 L. The ASAT was 7.92 L with a CV of 2.98% and a CR of 0.46 L. There was no significant difference in the semiautomated and manually segmented VAT (P = 0.73) but there were differences in the reliability of the two techniques. The mean semiautomated VAT was 2.56 L, CV 1.8%, and CR 0.09 L compared to the mean manually segmented VAT of 3.12 L, where the CV was 6.3% and the CR was 0.39 L. CONCLUSION: Rapid semiautomated whole body and compartmental fat volume quantification can be derived from a widebore 3T system, for a range of body sizes including obese patients, with "almost perfect" test-retest reliability. J. Magn. Reson. Imaging 2016;44:1464-1473.

Pharmacokinetic modeling of multislice dynamic contrast-enhanced MRI in normal-healing radial fractures: A pilot study.

PURPOSE: To define the range of quantitative pharmacokinetic parameters in normal-healing bone with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI is an established technique for characterizing abnormal tissue microvasculature within solid tumors, but has also shown promise for assessing bone and bone marrow. MATERIALS AND METHODS: In this study ethical approval for eight patients was obtained. Inclusion criteria were an extra-articular distal radial fracture in patients aged 20-50 years which had united by 6 weeks in plaster cast. This was assessed by an experienced orthopedic surgeon. DCE-MRI was performed at 1.5T 6 weeks after initial injury. The transfer constant (K(trans) ), transfer rate (Kep ), and initial area under the curve (IAUC) values for the fracture site and adjacent marrow were obtained for each patient. RESULTS: The mean T1 , K(trans) , Kep , and IAUC at the fracture site were 1713 (standard deviation [SD] 645), 0.09 (SD 0.07), 0.17 (SD 0.17) and 4.9 (SD 4.4). The relative standard deviation (RSD) for the fracture site ranged from 0.38 to 0.97 and for the adjacent marrow ranged from 0.95-3.88. Within each patient the range of RSDs was 0.04-0.42 for T1 , 0.26-0.91 for K(trans) , 0.14-1.06 for Kep , and 0.35-0.96 for the IAUC. CONCLUSION: Pharmacokinetic measures of perfusion can be obtained from healing fractures using DCE-MRI with "excellent" intraclass correlation coefficients for inter- and intrarater reliability. The use of these perfusion parameters is limited by wide patient-to-patient variation and slice-to-slice variation within patients.

Test-retest reliability of automated whole body and compartmental muscle volume measurements on a wide bore 3T MR system.

PURPOSE: To measure the test-retest reproducibility of an automated system for quantifying whole body and compartmental muscle volumes using wide bore 3 T MRI. MATERIALS AND METHODS: Thirty volunteers stratified by body mass index underwent whole body 3 T MRI, two-point Dixon sequences, on two separate occasions. Water-fat separation was performed, with automated segmentation of whole body, torso, upper and lower leg volumes, and manually segmented lower leg muscle volumes. RESULTS: Mean automated total body muscle volume was 19·32 L (SD9·1) and 19·28 L (SD9·12) for first and second acquisitions (Intraclass correlation coefficient (ICC) = 1·0, 95% level of agreement -0·32-0·2 L). ICC for all automated test-retest muscle volumes were almost perfect (0·99-1·0) with 95% levels of agreement 1.8-6.6% of mean volume. Automated muscle volume measurements correlate closely with manual quantification (right lower leg: manual 1·68 L (2SD0·6) compared to automated 1·64 L (2SD 0·6), left lower leg: manual 1·69 L (2SD 0·64) compared to automated 1·63 L (SD0·61), correlation coefficients for automated and manual segmentation were 0·94-0·96). CONCLUSION: Fully automated whole body and compartmental muscle volume quantification can be achieved rapidly on a 3 T wide bore system with very low margins of error, excellent test-retest reliability and excellent correlation to manual segmentation in the lower leg. KEY POINTS: Sarcopaenia is an important reversible complication of a number of diseases. Manual quantification of muscle volume is time-consuming and expensive. Muscles can be imaged using in and out of phase MRI. Automated atlas-based segmentation can identify muscle groups. Automated muscle volume segmentation is reproducible and can replace manual measurements.

Impact of source data on the interpretation of contrast-enhanced magnetic resonance angiography of the lower limbs.

BACKGROUND: The primary purpose of this study is to examine whether use of source data is effective in increasing the number of arterial segments that can be interpreted from maximum intensity projections of lower limb MR angiograms. Correlation between sites of arterial disease and venous contamination was also measured. Interpretation of source data is performed routinely by radiologists, but the value of this has not been well studied with randomized studies. RESULTS: The proportion of segments visible above the knee was 87% using maximal intensity projection alone (MIP) and 88% when the MIP was combined with source data. The proportions were 67% for MIP and 72% for MIP plus source data below the knee. There was substantial agreement between presence of arterial disease and venous contamination in the calf and thigh. CONCLUSION: The use of source data increases the number of assessable segments, but not individuals, by a statistically significant but small amount (1.2%, p <0.05). This study supports the association between arterial disease and venous contamination.

Developing a new measure of small bowel peristalsis with dynamic MR: a proof of concept study.

BACKGROUND: Small bowel peristalsis is a complex of many individual motion elements. Although each element of peristalsis can be measured there is no current global measure of peristalsis. PURPOSE: To examine the feasibility of automated computerized assessment of global small bowel motility using simple computational methods. MATERIAL AND METHODS: Coronal dynamic MR images were obtained from five healthy volunteers who had fasted for 9 h and drunk 1.5 L of water. Images were taken using single breath-hold and ECG triggering. Acquisitions were repeated at 10 and 20 min after an intramuscular injection of hyoscine butylbromide. Parametric maps were generated representing the mean change in signal amplitude (MSA) per voxel for each dynamic acquisition. Two observers independently assessed thresholding for optimal segmentation of small bowel from other sources of signal. Total voxel activity (TVA) for each study was calculated as a sum of MSA per slice and whole examination and TVA profiles were generated. RESULTS: Independent observations suggest that the automated segmentation method described usefully segments small bowel activity from other signal. Small bowel movement represented as TVA varied three-fold in the five volunteers and was inhibited by anti-muscarinic injection. CONCLUSION: It is possible to develop a new measure, based on automated segmentation of mean signal amplitude changes, of small bowel peristalsis using dynamic MR.

Advantages of blood pool contrast agents in MR angiography: a pictorial review.

Gadofosveset trisodium (Ablavar®, formerly Vasovist®) is the first intravascular contrast agent approved for clinical use in peripheral vascular disease. The purpose of this review is to illustrate the clinical uses of gadofosveset-enhanced magnetic resonance angiography in patients referred for assessment of arteriovenous disease. Superior T1 shortening enables first pass renal and peripheral arteriography of quality comparable with larger doses of extracellular agents. In applications such as thoracic outlet syndrome, there may be other advantages such as superior venous imaging and need for only one injection. Steady-state delayed imaging provides high resolution mapping of both arterial and venous systems and imaging of multiple territories. A combination of dynamic and delayed steady-state imaging can provide detailed anatomy and flow characteristics of vascular malformations and mapping for percutaneous sclerotherapy at one investigation. The ability to image in the steady state can provide minimally invasive imaging of thrombo-occlusive disease of central veins.

Physiology of the small bowel: a new approach using MRI and proposal for a new metric of function.

BACKGROUND: The mechanics of small bowel motility are extremely complex. Routine clinical access to small bowel has been restricted to radiological enteric contrast studies which have not contributed significantly to the understanding of small bowel physiology. Small bowel mechanics are understood within a framework of individual visible or measurable elements such as peristaltic wave formation, intra-luminal pressure gradients and transit times. There are no global measures of small bowel function that can be readily obtained in vivo in humans. Magnetic resonance imaging (MRI) is playing an increasingly important role in radiological diagnosis of small bowel disease and dynamic MRI offers the possibility of capturing small bowel movement in three-dimensional cinematic datasets. The metrics that are used to describe small bowel mechanics, typically anatomical measures in isolated segments, are not suited to analysing these large dynamic datasets. The proposal in this paper is to leave behind all previously described anatomical metrics and to describe anew the mechanics of small bowel movement in mathematical terms derived from changes in pixel intensity within dynamic MRI datasets so that global small bowel activity might be summarised in a single novel metric. HYPOTHESIS: The hypothesis of this paper is that global small bowel activity can be quantified by a new dynamic MR based metric. EVALUATION: A proposed strategy for evaluation includes a progression through feasibility, optimisation, reliability and validation studies. Thereafter normal volunteers would be required in order to define normal ranges for the new metric. These ranges would describe small bowel activity during fasting or after ingestion of fluids and standard meals. Mathematical modelling of the data could follow a two stage approach. The first stage could be to study segmentation or extraction techniques by which the small bowel activity could be isolated from MRI signal generated by the rest of the abdomen. The second stage would be to apply a number of data mining techniques that would identify significant features within the datasets. CONCLUSION: If this approach proves to be a useful model for studying small bowel physiology in humans, it would afford significant new avenues of research and treatment particularly in areas such as enteric drug delivery, the ageing gut, and nutrition.