Predictive accuracy of single‐ and multi‐slice MRI for the estimation of total visceral adipose tissue in overweight to severely obese patients

The quantification of visceral adipose tissue (VAT) is increasingly being considered for risk assessment and treatment monitoring in obese patients, but is generally time‐consuming. The goals of this work were to semi‐automatically segment and quantify VAT areas of MRI slices at previously proposed anatomical landmarks and to evaluate their predictive power for whole‐abdominal VAT volumes on a relatively large number of patients. One‐hundred and ninety‐seven overweight to severely obese patients (65 males; body mass index, 33.3 ± 3.5 kg/m²; 132 females; body mass index, 34.3 ± 3.2 kg/m²) underwent MRI examination. Total VAT volumes (V_VAT‐T) of the abdominopelvic cavity were quantified by retrospective analysis of two‐point Dixon MRI data (active‐contour segmentation, visual correction and histogram analysis). V_VAT‐T was then compared with VAT areas determined on one or five slices defined at seven anatomical landmarks (lumbar intervertebral spaces, umbilicus and femoral heads) and corresponding conversion factors were determined. Statistical measures were the coefficients of variation and standard deviations σ₁ and σ₅ of the difference between predicted and measured VAT volumes (Bland–Altman analysis). V_VAT‐T was 6.0 ± 2.0 L (2.5–11.2 L) for males and 3.2 ± 1.4 L (0.9–7.7 L) for females. The analysis of five slices yielded a better agreement than the analysis of single slices, required only a little extra time (4 min versus 2 min) and was substantially faster than whole‐abdominal assessment (24 min). Best agreements were found at intervertebral spaces L3–L4 for females (σ_5/1 = 523/608 mL) and L2–L3 for males (σ_5/1 = 613/706 mL). Five‐slice VAT volume estimates at the level of lumbar disc L3–L4 for females and L2–L3 for males can be obtained within 4 min and were a reliable predictor for abdominopelvic VAT volume in overweight to severely adipose patients. One‐slice estimates took only 2 min and were slightly less accurate. These findings may contribute to the implementation of analytical methods for fast and reliable (routine) estimation of VAT volumes in obese patients. Copyright © 2015 John Wiley & Sons, Ltd.     

Variability in fasting lipid and glycogen contents in hepatic and skeletal muscle tissue in subjects with and without type 2 diabetes: a 1H and 13C MRS study

The measurement of tissue lipid and glycogen contents and the establishment of normal levels of variability are important when assessing changes caused by pathology or treatment. We measured hepatic and skeletal muscle lipid and glycogen levels using ¹H and ¹³C MRS at 3 T in groups of subjects with and without type 2 diabetes. Within‐visit reproducibility, due to repositioning and instrument errors was determined from repeat measurements made over 1 h. Natural variability was assessed from separate measurements made on three occasions over 1 month. Hepatic lipid content was greater in subjects with diabetes relative to healthy subjects (p = 0.03), whereas levels of hepatic and skeletal muscle glycogen, and of intra‐ and extra‐myocellular lipid, were similar. The single‐session reproducibility values (coefficient of variation, CV) for hepatic lipid content were 12% and 7% in groups of subjects with and without diabetes, respectively. The variability of hepatic lipid content over 1 month was greater than the reproducibility, with CV = 22% (p = 0.08) and CV = 44% (p = 0.004) in subjects with and without diabetes, respectively. Similarly, levels of variation in basal hepatic glycogen concentrations (subjects with diabetes, CV = 38%; healthy volunteers, CV = 35%) were significantly larger than single‐session reproducibility values (CV = 17%, p = 0.02 and CV = 13%, p = 0.05, respectively), indicating substantial biological changes in basal concentrations over 1 month. There was a decreasing correlation in measurements of both hepatic lipid and glycogen content with increasing time between scans. Levels of variability in intra‐ and extra‐myocellular lipid in the soleus muscle, and glycogen concentrations in the gastrocnemius muscle, tended to be larger than expected from single‐session reproducibility, although these did not reach significance. Copyright © 2013 John Wiley & Sons, Ltd.     

Stability and sensitivity of water T2 obtained with IDEAL‐CPMG in healthy and fat‐infiltrated skeletal muscle

Quantifying muscle water T₂ (T₂‐water) independently of intramuscular fat content is essential in establishing T₂‐water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL‐CPMG combines chemical shift fat–water separation with T₂ relaxometry to obtain such a measure. Here we evaluate the reproducibility and B₁ sensitivity of IDEAL‐CPMG T₂‐water and fat fraction (f.f.) values in healthy subjects, and demonstrate the potential of the method to quantify T₂‐water variation in diseased muscle displaying varying degrees of fatty infiltration. The calf muscles of 11 healthy individuals (40.5 ± 10.2 years) were scanned twice at 3 T with an inter‐scan interval of 4 weeks using IDEAL‐CPMG, and 12 patients with hypokalemic periodic paralysis (HypoPP) (42.3 ± 11.5 years) were also imaged. An exponential was fitted to the signal decay of the separated water and fat components to determine T₂‐water and the fat signal amplitude muscle regions manually segmented. Overall mean calf‐level muscle T₂‐water in healthy subjects was 31.2 ± 2.0 ms, without significant inter‐muscle differences (p = 0.37). Inter‐subject and inter‐scan coefficients of variation were 5.7% and 3.2% respectively for T₂‐water and 41.1% and 15.4% for f.f. Bland–Altman mean bias and ±95% coefficients of repeatability were for T₂‐water (0.15, ?2.65, 2.95) ms and f.f. (?0.02, ?1.99, 2.03)%. There was no relationship between T₂‐water (ρ = 0.16, p = 0.07) or f.f. (ρ = 0.03, p = 0.7761) and B₁ error or any correlation between T₂‐water and f.f. in the healthy subjects (ρ = 0.07, p = 0.40). In HypoPP there was a measurable relationship between T₂‐water and f.f. (ρ = 0.59, p < 0.001). IDEAL‐CPMG provides a feasible way to quantify T₂‐water in muscle that is reproducible and sensitive to meaningful physiological changes without post hoc modeling of the fat contribution. In patients, IDEAL‐CPMG measured elevations in T₂‐water and f.f. while showing a weak relationship between these parameters, thus showing promise as a practical means of quantifying muscle water in patient populations.     

Tractography of the optic radiation: a repeatability and reproducibility study

Our main objective was to evaluate the repeatability and reproducibility of optic radiation (OR) reconstruction from diffusion MRI (dMRI) data. 14 adults were scanned twice with the same 60‐direction dMRI sequence. Peaks in the diffusion profile were estimated with the single tensor (ST), Q‐ball (QSH) and persistent angular structure (PAS) methods. Segmentation of the OR was performed by two experimenters with probabilistic tractography based on a manually drawn region‐of‐interest (ROI) protocol typically employed for OR segmentation, with both standard and extended sets of ROIs. The repeatability and reproducibility were assessed by calculating the intra‐class correlation coefficient (ICC) of intra‐ and inter‐rater experiments, respectively. ICCs were calculated for commonly used dMRI metrics (FA, MD, AD, RD) and anatomical dimensions of the optic radiation (distance from Meyer's loop to the temporal pole, ML‐TP), as well as the Dice similarity coefficient (DSC) between the raters’ OR segmentation. Bland–Altman plots were also calculated to investigate bias and variability in the reproducibility measurements. The OR was successfully reconstructed in all subjects by both raters. The ICC was found to be in the good to excellent range for both repeatability and reproducibility of the dMRI metrics, DSC and ML‐TP distance. The Bland–Altman plots did not show any apparent systematic bias for any quantities. Overall, higher ICC values were found for the multi‐fiber methods, QSH and PAS, and for the standard set of ROIs. Considering the good to excellent repeatability and reproducibility of all the quantities investigated, these findings support the use of multi‐fiber OR reconstruction with a limited number of manually drawn ROIs in clinical applications utilizing either OR microstructure characterization or OR dimensions, as is the case in neurosurgical planning for temporal lobectomy. Copyright © 2015 John Wiley & Sons, Ltd.     

Multi‐parametric MRI characterization of healthy human thigh muscles at 3.0 T – relaxation,magnetization transfer,fat/water,and diffusion tensor imaging

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo‐pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin‐echo T₂ imaging (with and without fat signal suppression, FS), selective inversion recovery for T₁ and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re‐imaged an average of 35 days later. Pre‐testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between‐day intra‐class correlations were observed in all quantitative indices except for the macromolecular‐to‐free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two‐way analysis of variance revealed no significant between‐day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland–Altman plots, and low repeatability coefficients were obtained for all parameters. Among‐muscle differences in the quantitative MRI indices and inter‐class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T₁, T₂, fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters. Copyright © 2014 John Wiley & Sons, Ltd.     

Repeatability of a dual gradient‐recalled echo MRI method for monitoring post‐isometric contraction blood volume and oxygenation changes

The purpose of this study was to assess the repeatability of a dual gradient‐recalled echo (GRE) muscle functional MRI technique. On 2 days, subjects (n = 8) performed 10 s isometric dorsiflexion contractions under conditions of: (1) maximal voluntary contraction (MVC), (2) 50% MVC (50% MVC), or (3) 50% MVC with concurrent proximal arterial cuff occlusion (50% MVC_cuff). Functional MRI data were acquired using single‐slice dual GRE (TR/TE = 1000/6, 46 ms)‐echo planar imaging for 20 s before, during, and for 180 s after each contraction. The mean signal intensity (SI) time courses at each TE (SI₆ and SI₄₆, reflecting variations in blood volume and %HbO₂, respectively) from the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles were characterized with the post‐contraction change in SI and the time‐to‐peak SI (ΔSI and TTP, respectively). ΔSI₆ following an MVC was 36% higher than that obtained after a 50% MVC (p = 0.048). For ΔSI₆, the highest intraclass correlation coefficients (ICCs) were observed for the TA muscle in the 50% MVC and MVC conditions, with values of 0.83 (p = 0.01) and 0.88 (p = 0.005), respectively. Bland–Altman plots revealed repeatability coefficients (RCs) for the 50% MVC and MVC conditions in the TA muscle of 1.9 and 1.4, respectively. The most repeatable measures for ΔSI₄₆ were obtained for the 50% MVC and MVC conditions in the EDL muscle (p = 0.01 and p = 0.04, respectively). Bland–Altman plots revealed RC's for 50% MVC and MVC conditions in the EDL muscle of 3.9 and 5.7, respectively. ΔSI₆ and ΔSI₄₆ increased as a function of the contraction intensity. The repeatability of the method depends on the muscle and contraction condition being evaluated, and in general, is higher following an MVC. Copyright © 2009 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI of breast lesions: a prospective clinical investigation of the quantitative imaging biomarker characteristics of reproducibility,repeatability, and diagnostic accuracy

Diffusion‐weighted MRI (DWI) provides insights into tissue microstructure by visualization and quantification of water diffusivity. Quantitative evaluation of the apparent diffusion coefficient (ADC) obtained from DWI has been proven helpful for differentiating between malignant and benign breast lesions, for cancer subtyping in breast cancer patients, and for prediction of response to neoadjuvant chemotherapy. However, to further establish DWI of breast lesions it is important to evaluate the quantitative imaging biomarker (QIB) characteristics of reproducibility, repeatability, and diagnostic accuracy. In this intra‐individual prospective clinical study 40 consecutive patients with suspicious findings, scheduled for biopsy, underwent an identical 3T breast MRI protocol of the breast on two consecutive days (>24 h). Mean ADC of target lesions was assessed (two independent readers) in four separate sessions. Reproducibility, repeatability, and diagnostic accuracy between examinations (E1, E2), readers (R1, R2), and measurements (M1, M2) were assessed with intraclass correlation coefficients (ICCs), coefficients of variation (CVs), Bland–Altman plots, and receiver operating characteristic (ROC) analysis with calculation of the area under the ROC curve (AUC). The standard of reference was either histopathology (n = 38) or imaging follow‐up of up to 24 months (n = 2). Eighty breast MRI examinations (median E1–E2, 2 ± 1.7 days, 95% confidence interval (CI) 1–2 days, range 1–11 days) in 40 patients (mean age 56, standard deviation (SD) ±14) were evaluated. In 55 target lesions (mean size 25.2 ± 20.8 (SD) mm, range 6–106 mm), mean ADC values were significantly (P < 0.0001) higher in benign (1.38, 95% CI 1.27–1.49 × 10^?3 mm²/s) compared with malignant (0.86, 95% CI 0.81–0.91 × 10^?3 mm²/s) lesions. Reproducibility and repeatability showed high agreement for repeated examinations, readers, and measurements (all ICCs >0.9, CVs 3.2–8%), indicating little variation. Bland–Altman plots demonstrated no systematic differences, and diagnostic accuracy was not significantly different in the two repeated examinations (all ROC curves >0.91, P > 0.05). High reproducibility, repeatability, and diagnostic accuracy of DWI provide reliable characteristics for its use as a potential QIB, to further improve breast lesion detection, characterization, and treatment monitoring of breast lesions.     

Influence of fat–water separation and spatial resolution on automated volumetric MRI measurements of fibroglandular breast tissue

The aim of this study was to investigate the influence of fat–water separation and spatial resolution in MRI on the results of automated quantitative measurements of fibroglandular breast tissue (FGT). Ten healthy volunteers (age range, 28–71 years; mean, 39.9 years) were included in this Institutional Review Board‐approved prospective study. All measurements were performed on a 1.5‐T scanner (Siemens, AvantoFit) using an 18‐channel breast coil. The protocols included isotropic (Di) [TR/TE₁/TE₂ = 6.00 ms/2.45 ms/2.67 ms; flip angle, 6.0°; 256 slices; matrix, 360 × 360; 1 mm isotropic; field of view, 360°; acquisition time (TA) = 3 min 38 s] and anisotropic (Da) (TR/TE₁/TE₂ = 10.00 ms/2.39 ms/4.77 ms; flip angle, 24.9°; 80 slices; matrix 360 × 360; voxel size, 0.7 × 0.7 × 2.0 mm³; field of view, 360°; TA = 1 min 25 s) T₁ three‐dimensional (3D) fast low‐angle shot (FLASH) Dixon sequences, and a T₁ 3D FLASH sequence with the same resolution (T₁) without (TR/TE = 11.00 ms/4.76 ms; flip angle, 25.0°; 80 slices; matrix, 360 × 360; voxel size, 0.7 × 0.7 × 2.0 mm³; field of view, 360°; TA = 50 s) and with (TR/TE = 29.00 ms/4.76 ms; flip angle, 25.0°; 80 slices; matrix, 360 × 360; voxel size, 0.7 × 0.7 × 2.0 mm³; field of view, 360°; TA = 2 min 35 s) fat saturation. Repeating volunteer measurements after 20 min and repositioning were used to assess reproducibility. An automated and quantitative volumetric breast density measurement system was used for FGT calculation. FGT with Di, Da and T₁ measured 4.6–63.0% (mean, 30.6%), 3.2–65.3% (mean, 32.5%) and 1.7–66.5% (mean, 33.7%), respectively. The highest correlation between different MRI sequences was found with the Di and Da sequences (R² = 0.976). Coefficients of variation (CVs) for FGT calculation were higher in T₁ (CV = 21.5%) compared with Dixon (Di, CV = 5.1%; Da, CV = 4.2%) sequences. Dixon‐type sequences worked well for FGT measurements, even at lower resolution, whereas the conventional T₁‐weighted sequence was more sensitive to decreasing resolution. The Dixon fat–water separation technique showed superior repeatability of FGT measurements compared with conventional sequences. A standard dynamic protocol using Dixon fat–water separation is best suited for combined diagnostic purposes and prognostic measurements of FGT. Copyright © 2016 John Wiley & Sons, Ltd.     

Endometrial cell counts in recurrent miscarriage: a comparison of counting methods

Drury J A, Nik H, van Oppenraaij R H F, Tang A‐W, Turner M A & Quenby S
(2011 Histopathology  59 , 1156–1162
Endometrial cell counts in recurrent miscarriage: a comparison of counting methods Aims: Studies of uterine natural killer (uNK) cells require reliable measurements of uNK cell density among diverse endometrial tissue. The aim of this study was to compare cell counting manually with two computer‐aided methods based on a public domain software package, ImageJ. Methods and results: Immunohistochemistry (IHC) of CD56⁺ uNK cells was performed on endometrium from recurrent miscarriage patients. Numbers of stromal cells per high‐power field (HPF) were counted by two observers using: (i) manual tally counter and graticule; (ii) ImageJ ‘point picker’ tool; and (iii) ImageJ ‘particle analysis’ tool. Coefficients of variation (CV) and Bland–Altman plots were used to evaluate interobserver differences. Evaluation of %uNK using ImageJ particle analysis for stromal cell counts and point picker tool for uNK counts was undertaken. Point picker and particle analysis were significantly better than manual counting [interobserver CVs mean (standard deviation) 6.1% (3.3%); 4.7% (3.9%), 8.2% (6.5%), respectively]. Mean inter‐ and intra‐observer CVs for %uNK were 10.3% (6.6%), 8.5% (4.9%) and 6.8% (4.3%), respectively. Bland–Altman analysis revealed no systematic differences in cell counts with the number of cells in the image for each method. Conclusions: Compared to manual cell counting, computer‐aided image analysis yields more reproducible results for the assessment of uNK cells density using IHC.     

Hepatic arterial spin labelling MRI: an initial evaluation in mice

The development of strategies to combat hepatic disease and augment tissue regeneration has created a need for methods to assess regional liver function. Liver perfusion imaging has the potential to fulfil this need, across a range of hepatic diseases, alongside the assessment of therapeutic response. In this study, the feasibility of hepatic arterial spin labelling (HASL) was assessed for the first time in mice at 9.4 T, its variability and repeatability were evaluated, and it was applied to a model of colorectal liver metastasis. Data were acquired using flow‐sensitive alternating inversion recovery‐arterial spin labelling (FAIR‐ASL) with a Look–Locker readout, and analysed using retrospective respiratory gating and a T₁‐based quantification. This study shows that preclinical HASL is feasible and exhibits good repeatability and reproducibility. Mean estimated liver perfusion was 2.2 ± 0.8 mL/g/min (mean ± standard error, n = 10), which agrees well with previous measurements using invasive approaches. Estimates of the variation gave a within‐session coefficient of variation (CV_WS) of 7%, a between‐session coefficient of variation (CV_BS) of 9% and a between‐animal coefficient of variation (CV_A) of 15%. The within‐session Bland–Altman repeatability coefficient (RC_WS) was 18% and the between‐session repeatability coefficient (RC_BS) was 29%. Finally, the HASL method was applied to a mouse model of liver metastasis, in which significantly lower mean perfusion (1.1 ± 0.5 mL/g/min, n = 6) was measured within the tumours, as seen by fluorescence histology. These data indicate that precise and accurate liver perfusion estimates can be achieved using ASL techniques, and provide a platform for future studies investigating hepatic perfusion in mouse models of disease. Copyright © 2014 John Wiley & Sons, Ltd.     

Repeatability of DTI‐based skeletal muscle fiber tracking

Diffusion tensor imaging (DTI)‐based muscle fiber tracking enables the measurement of muscle architectural parameters, such as pennation angle (θ) and fiber tract length (L_ft), throughout the entire muscle. Little is known, however, about the repeatability of either the muscle architectural measures or the underlying diffusion measures. Therefore, the goal of this study was to investigate the repeatability of DTI fiber tracking‐based measurements and θ and L_ft. Four DTI acquisitions were performed on two days that allowed for between acquisition, within day, and between day analyses. The eigenvalues and fractional anisotropy were calculated at the maximum cross‐sectional area of, and fiber tracking was performed in, the tibialis anterior muscle of nine healthy subjects. The between acquisitions condition had the highest repeatability for the DTI indices and the architectural parameters. The overall inter class correlation coefficients (ICC's) were greater than 0.6 for both θ and L_ft and the repeatability coefficients were θ < 10.2° and L_ft < 50 mm. In conclusion, under the experimental and data analysis conditions used, the repeatability of the diffusion measures is very good and repeatability of the architectural measurements is acceptable. Therefore, this study demonstrates the feasibility for longitudinal studies of alterations in muscle architecture using DTI‐based fiber tracking, under similar noise conditions and with similar diffusion characteristics. Copyright © 2010 John Wiley & Sons, Ltd.     

Multi‐centre reproducibility of diffusion MRI parameters for clinical sequences in the brain

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra‐voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice–water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub‐regions. A mixed effect model was used to measure the intra‐ and inter‐scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra‐ and inter‐scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra‐scanner CV of 8.4% and inter‐scanner CV of 24.8%. No major difference in the inter‐scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra‐scanner reproducibility, with the inter‐scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter‐scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi‐centre clinical studies and trials. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.     

Effects of exercise‐induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used ³¹P‐magnetic resonance spectroscopy (³¹P‐MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min^‐1, CV_{inter‐subject} = 42%) as compared with PF (46 ± 20 mM min^‐1, CV_{inter‐subject} = 44%) and tended to be higher in FF (43 ± 35 mM min^‐1, CV_{inter‐subject} = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end‐exercise pH in Q (p < 0.01), FF (p < 0.05) and PF (p <0.05) as well as proton efflux rate in FF (p < 0.01), PF (p < 0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end‐exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter‐ and intra‐individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates. Copyright © 2013 John Wiley & Sons, Ltd.     

Simultaneous use of linear and nonlinear gradients for B1+ inhomogeneity correction

The simultaneous use of linear spatial encoding magnetic fields (L‐SEMs) and nonlinear spatial encoding magnetic fields (N‐SEMs) in B₁⁺ inhomogeneity problems is formulated and demonstrated with both simulations and experiments. Independent excitation k‐space variables for N‐SEMs are formulated for the simultaneous use of L‐SEMs and N‐SEMs by assuming a small tip angle. The formulation shows that, when N‐SEMs are considered as an independent excitation k‐space variable, numerous different k‐space trajectories and frequency weightings differing in dimension, length, and energy can be designed for a given target transverse magnetization distribution. The advantage of simultaneous use of L‐SEMs and N‐SEMs is demonstrated by B₁⁺ inhomogeneity correction with spoke excitation. To fully utilize the independent k‐space formulations, global optimizations are performed for 1D, 2D RF power limited, and 2D RF power unlimited simulations and experiments. Three different cases are compared: L‐SEMs alone, N‐SEMs alone, and both used simultaneously. In all cases, the simultaneous use of L‐SEMs and N‐SEMs leads to a decreased standard deviation in the ROI compared with using only L‐SEMs or N‐SEMs. The simultaneous use of L‐SEMs and N‐SEMs results in better B₁⁺ inhomogeneity correction than using only L‐SEMs or N‐SEMs due to the increased number of degrees of freedom.     

Automated digital volume measurement of melanoma metastases in sentinel nodes predicts disease recurrence and survival

Riber‐Hansen R, Nyengaard J R, Hamilton‐Dutoit S J, Sjoegren P & Steiniche T
(2011) Histopathology 59 , 433–440 Automated digital volume measurement of melanoma metastases in sentinel nodes predicts disease recurrence and survival Aims: Total metastatic volume (TMV) is an important prognostic factor in melanoma sentinel lymph nodes (SLNs) that avoids both the interobserver variation and unidirectional upstaging seen when using semi‐quantitative size estimates. However, it is somewhat laborious for routine application. Our aim was to investigate whether digital image analysis can estimate TMV accurately in melanoma SLNs. Methods and results: TMV was measured in 147 SLNs from 95 patients both manually and by automated digital image analysis. The results were compared by Bland–Altman plots (numerical data) and kappa statistics (categorical data). In addition, disease‐free and melanoma‐specific survivals were calculated. Mean metastatic volume per patient was 10.6 mm³ (median 0.05 mm³; range 0.0001–621.3 mm³) and 9.62 mm³ (median 0.05 mm³; range 0.00001–564.3 mm³) with manual and digital measurement, respectively. The Bland–Altman plot showed an even distribution of the differences, and the kappa statistic was 0.84. In multivariate analysis, both manual and digital metastasis volume measurements were independent progression markers when corrected for primary tumour thickness [manual: hazard ratio (HR): 1.21, 95% confidence interval (CI): 1.07–1.36, P = 0.002; digital: HR: 1.21, 95% CI: 1.06–1.37, P = 0.004]. Conclusions: Stereology‐based, automated digital metastasis volume measurement in melanoma SLNs predicts disease recurrence and survival.     

Supervised segmentation framework for evaluation of diffusion tensor imaging indices in skeletal muscle

Diffusion tensor imaging (DTI) is becoming a relevant diagnostic tool to understand muscle disease and map muscle recovery processes following physical activity or after injury. Segmenting all the individual leg muscles, necessary for quantification, is still a time‐consuming manual process. The purpose of this study was to evaluate the impact of a supervised semi‐automatic segmentation pipeline on the quantification of DTI indices in individual upper leg muscles. Longitudinally acquired MRI datasets (baseline, post‐marathon and follow‐up) of the upper legs of 11 subjects were used in this study. MR datasets consisted of a DTI and Dixon acquisition. Semi‐automatic segmentations for the upper leg muscles were performed using a transversal propagation approach developed by Ogier et al on the out‐of‐phase Dixon images at baseline. These segmentations were longitudinally propagated for the post‐marathon and follow‐up time points. Manual segmentations were performed on the water image of the Dixon for each of the time points. Dice similarity coefficients (DSCs) were calculated to compare the manual and semi‐automatic segmentations. Bland‐Altman and regression analyses were performed, to evaluate the impact of the two segmentation methods on mean diffusivity (MD), fractional anisotropy (FA) and the third eigenvalue (λ₃). The average DSC for all analyzed muscles over all time points was 0.92 ± 0.01, ranging between 0.48 and 0.99. Bland‐Altman analysis showed that the 95% limits of agreement for MD, FA and λ₃ ranged between 0.5% and 3.0% for the transversal propagation and between 0.7% and 3.0% for the longitudinal propagations. Similarly, regression analysis showed good correlation for MD, FA and λ₃ (r = 0.99, p < 60; 0.0001). In conclusion, the supervised semi‐automatic segmentation framework successfully quantified DTI indices in the upper‐leg muscles compared with manual segmentation while only requiring manual input of 30% of the slices, resulting in a threefold reduction in segmentation time.     

Reduced respiratory motion artifacts using structural similarity in fast 2D dynamic contrast enhanced MRI of liver lesions

The purpose of this work was to improve dynamic contrast enhanced MRI (DCE‐MRI) of liver lesions by removing motion corrupted images as identified by a structural similarity (SSIM) algorithm, and to assess the effect of this correction on the pharmacokinetic parameter K^trans using automatically determined arterial input functions (AIFs). Fifteen patients with colorectal liver metastases were measured twice with a T₁ weighted multislice 2D FLASH sequence for DCE‐MRI (time resolution 1.2 s). AIFs were automatically derived from contrast inflow in the aorta of each patient. Thereafter, SSIM identified motion corrupted images of the liver were removed from the DCE dataset. From this corrected data set K^trans and its reproducibility were determined. Using the SSIM algorithm a median fraction of 46% (range 37–50%) of the liver images in DCE time series was labeled as motion distorted. Rejection of these images resulted in a significantly lower median K^trans (p < 0.05) and lower coefficient of repeatability of K^trans in liver metastases compared with an analysis without correction. SSIM correction improves the reproducibility of the DCE‐MRI parameter K^trans in liver metastasis and reduces contamination of K^trans values of lesions by that of surrounding normal liver tissue.     

The feasibility of quantitative MRI of extra‐ocular muscles in myasthenia gravis and Graves' orbitopathy

Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra‐ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye‐motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2_water) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2_water values were determined in 12 HC (aged 22‐65 years), 11 MG (aged 28‐71 years) and six GO (aged 28‐64 years) patients at 7 T using Dixon and multi‐echo spin‐echo sequences. The EOM were semi‐automatically 3D‐segmented by two independent observers. MANOVA and t‐tests were used to assess differences in FF, T2_water and volume of EOM between groups (P < .05). Bland–Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was ?0.7% (LoA: ±2.1%) for the different observers; the bias in FF was ?0.3% (LoA: ±2.8%) and 0.03 cm³ (LoA: ± 0.36 cm³) for volume. Mean FF of EOM in MG (14.1% ± 1.6%) was higher than in HC (10.4% ± 2.5%). Mean muscle volume was higher in both GO (1.2 ± 0.4 cm³) and MG (0.8 ± 0.2 cm³) compared with HC (0.6 ± 0.2 cm³). The average T2_water for all EOM was 24.6 ± 4.0 ms for HC, 24.0 ± 4.7 ms for MG patients and 27.4 ± 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2_water was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes.     

Magnetic resonance elastography of the lungs: A repeatability and reproducibility study

Lung diseases are one of the leading causes of death worldwide, from which four million people die annually. Lung diseases are associated with changes in the mechanical properties of the lungs. Several studies have shown the feasibility of using magnetic resonance elastography (MRE) to quantify the lungs' shear stiffness. The aim of this study is to investigate the reproducibility and repeatability of lung MRE, and its shear stiffness measurements, obtained using a modified spin echo‐echo planar imaging (SE‐EPI) MRE sequence. In this study, 21 healthy volunteers were scanned twice by repositioning the volunteers to image right lung both at residual volume (RV) and total lung capacity (TLC) to assess the reproducibility of lung shear stiffness measurements. Additionally, 19 out of the 21 volunteers were scanned immediately without moving the volunteers to test the repeatability of the modified SE‐EPI MRE sequence. A paired t‐test was performed to determine the significant difference between stiffness measurements obtained at RV and TLC. Concordance correlation and Bland–Altman's analysis were performed to determine the reproducibility and repeatability of the SE‐EPI MRE‐derived shear stiffness measurements. The SE‐EPI MRE sequence is highly repeatable with a concordance correlation coefficient (CCC) of 0.95 at RV and 0.96 at TLC. Similarly, the stiffness measurements obtained across all volunteers were highly reproducible with a CCC of 0.95 at RV and 0.92 at TLC. The mean shear stiffness of the lung at RV was 0.93 ± 0.22 kPa and at TLC was 1.41 ± 0.41 kPa. TLC showed a significantly higher mean shear stiffness (P = 0.0004) compared with RV. Lung MRE stiffness measurements obtained using the SE‐EPI sequence were reproducible and repeatable, both at RV and TLC. Lung shear stiffness changes across respiratory cycle with significantly higher stiffness at TLC than RV.