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.     

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.     

No non-sentinel node involvement in melanoma patients with limited Breslow thickness and low sentinel node tumour load

Bogenrieder T, van Dijk M R, Blokx W A M, Ramrath K, Seldenrijk K, Stolz W & van Diest P J
(2011) Histopathology 59 , 318–326 No non‐sentinel node involvement in melanoma patients with limited Breslow thickness and low sentinel node tumour load Aims: Most melanoma patients with a positive sentinel node (SN) undergo completion lymph node dissection and frequently experience associated morbidity. However, only 10–30% of SN‐positive patients have further lymph node metastases. The aim of the present study was to predict the absence of non‐SN metastases in a multicentre study of patients with a positive SN based on primary melanoma features and SN tumour load. Methods and results: Of 70 SN positive patients, 18 had non‐SN metastases. Penetrative depth of metastatic cells into the SN and SN tumour load was assessed by morphometry. None of the 14 patients (20%) with a Breslow thickness <2.0 mm and an SN tumour load <0.2 mm² had non‐SN metastases. Similarly, none of the 15 patients (21%) with a Breslow thickness <2.0 mm and SN penetrative depth <600 μm had non‐SN metastases. Lastly, none of the 14 patients (20%) with a Breslow thickness <2.0 mm and a diameter of the largest SN deposit <500 μm had non‐SN metastases. Conclusions: A combination of limited Breslow thickness and low SN tumour load predicts absence of non‐SN metastases in melanoma patients with a positive SN with high accuracy. We propose that this subgroup may be spared completion lymph node dissection.     

Comparison of actigraphy with polysomnography and sleep logs in depressed insomniacs

Actigraphy is increasingly used in the assessment and treatment of various clinical conditions, being a convenient and cost‐effective method of capturing bodily movements over long periods of time. This study examined the use of actigraphy in the measurement of sleep of patients with depression and insomnia. Fifty‐four patients diagnosed with a current major depressive episode and chronic insomnia underwent a baseline overnight study with concurrent actigraphic and polysomnography (PSG) monitoring, as well as subjective sleep diaries. Agreement between PSG, actigraphy and sleep diary measurements was evaluated using two‐tailed t‐tests, Pearson’s correlations and the Bland–Altman concordance technique. The only significant difference found between actigraphy and PSG was in latency to persistent sleep, in which actigraphy underestimated sleep latency relative to PSG (P < 0.05). There were moderate positive correlations between actigraphy and PSG for all variables. In contrast, significant differences were observed between sleep diaries and PSG for all sleep variables. Bland–Altman concordance diagrams also demonstrated that, while bias was limited between PSG and the other two measurement types, there were somewhat broad 95% limits of agreement for all sleep variables with both sleep diaries and actigraphy. In summary, actigraphic measurements of sleep more closely approximated those of PSG than did sleep diaries in this sample of depressed insomniacs.     

Accelerated three‐dimensional cine phase contrast imaging using randomly undersampled echo planar imaging with compressed sensing reconstruction

The aim of this study was to implement and evaluate an accelerated three‐dimensional (3D) cine phase contrast MRI sequence by combining a randomly sampled 3D k‐space acquisition sequence with an echo planar imaging (EPI) readout. An accelerated 3D cine phase contrast MRI sequence was implemented by combining EPI readout with randomly undersampled 3D k‐space data suitable for compressed sensing (CS) reconstruction. The undersampled data were then reconstructed using low‐dimensional structural self‐learning and thresholding (LOST). 3D phase contrast MRI was acquired in 11 healthy adults using an overall acceleration of 7 (EPI factor of 3 and CS rate of 3). For comparison, a single two‐dimensional (2D) cine phase contrast scan was also performed with sensitivity encoding (SENSE) rate 2 and approximately at the level of the pulmonary artery bifurcation. The stroke volume and mean velocity in both the ascending and descending aorta were measured and compared between two sequences using Bland–Altman plots. An average scan time of 3 min and 30 s, corresponding to an acceleration rate of 7, was achieved for 3D cine phase contrast scan with one direction flow encoding, voxel size of 2 × 2 × 3 mm³, foot–head coverage of 6 cm and temporal resolution of 30 ms. The mean velocity and stroke volume in both the ascending and descending aorta were statistically equivalent between the proposed 3D sequence and the standard 2D cine phase contrast sequence. The combination of EPI with a randomly undersampled 3D k‐space sampling sequence using LOST reconstruction allows a seven‐fold reduction in scan time of 3D cine phase contrast MRI without compromising blood flow quantification. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Monitoring intracellular, interstitial, and intravascular volume changes during fluid management procedures

The bioimpedance spectroscopic (BIS) analytical algorithm described in this report allows for the non-invasive measurement of intravascular, interstitial, and intracellular volume changes during various fluid management procedures. The purpose of this study was to test clinical use feasibility and to demonstrate the validity of the BIS algorithm in computing compartmental volume shifts in human subjects undergoing fluid management treatment. Validation was performed using volume changes recorded from 20 end stage renal disease patients. The validation procedure involved mathematically deriving post hoc hematocrit profiles from the BIS data-generated fluid redistribution time profiles. These derived hematocrit profiles were then compared to serial hematocrit values measured simultaneously by a CritLine^® monitor during 60 routine hemodialysis sessions. Regression and Bland–Altman analyses confirm that the BIS algorithm can be used to reliably derive the continuous and real-time rates of change of the compartmental fluid volumes. Regression results yielded a R ² > 0.99 between the two measures of hematocrit at different times during dialysis. The slopes of the regression equations at the different times were nearly identical, demonstrating an almost one-to-one correspondence between the BIS and CritLine^® hematocrits. Bland–Altman analysis show that the BIS algorithm can be used interchangeably with the CritLine^® monitor for the measurement of hematocrit. The present study demonstrates for the first time that BIS can provide real-time continuous measurements of compartmental intravascular, interstitial and intracellular fluid volume changes during fluid management procedures when used in conjunction with this new algorithm.     

Assessing the variability of 23Na MRI in skeletal muscle tissue: Reproducibility and repeatability of tissue sodium concentration measurements in the lower leg at 3 T

The goal of this study was to evaluate the reproducibility and repeatability of tissue sodium concentration (TSC) measurements using ²³Na MRI in skeletal muscle tissue. ²³Na MRI was performed at 3 T on the right lower leg of eight healthy volunteers (aged 28 ± 4 years). The examinations were repeated at the same site after ~ 22 weeks to assess the variability over a medium‐term period. Additionally, they were scanned at a second site shortly before or shortly after the first visit (within 3 weeks) to evaluate the inter‐site reproducibility. Moreover, we analysed the effect of B₀ correction on the variability. Coefficients of variations (CVs) from mean TSC values as well as Bland–Altman plots were used to assess intra‐site repeatability and inter‐site reproducibility. In phantom measurements, the B₀ correction improved the quantitative accuracy. We observed differences of up to 4.9 mmol/L between the first and second visit and a difference of up to 3.7 mmol/L between the two different sites. The CV for the medium‐term repeatability was 15% and the reproducibility CV was 9%. The Bland–Altman plots indicated high agreement between the visits in all muscle regions. The systematic bias of ?0.68 mmol/L between site X and Y (P = 0.03) was slightly reduced to ?0.64 mmol/L after B₀ correction (P = 0.04). This work shows that TSC measurements in healthy skeletal muscle tissue can be performed with good repeatability and reproducibility, which is of importance for future longitudinal or multicentre studies.     

Comparison of field methods to estimate fat mass in children

Background: Reliable field methods to measure fat mass (FM) in children may contribute to primary prevention of childhood obesity.

Aim: The objective was to compare the accuracy of existing field methods (skinfold thickness (SF), leg-to-leg bioelectrical impedance analysis (BIA), anthropometrics for FM measurement in prepubertal European children.

Subjects and methods: Reference FM was measured in 55 French children (30 boys, 25 girls; mean age 8.7 years) using a three-compartment model: body volume (BV) was assessed by air displacement plethysmography (ADP) and total body water (TBW) was assessed by deuterium dilution. Agreement between field methods and the reference method was assessed using Bland–Altman analyses. Since field methods for FM measurement are reported to be population-dependent, adjustment to the study population was performed using stepwise multiple linear regressions modelling.

Results: Even after adjustment, field methods exhibited a high correlation (R²?=?0.71–0.84) but a moderate agreement (±3.32 to ±4.47 kg for fat mass) with the reference model. Methods based on BIA or SF performed slightly better than those based on anthropometry.

Conclusions: Field methods for FM measurement may be recommended for epidemiological applications, but not for individual follow-up. New field equipment is required to improve accuracy of FM measurement in children and make individual follow-up possible.     

Simultaneous evaluation of vascular morphology,blood volume and transvascular permeability using SPION‐based,dual‐contrast MRI: imaging optimization and feasibility test

Exploiting ultrashort‐T_E (UTE) MRI, T₁‐weighted positive contrast can be obtained from superparamagnetic iron oxide nanoparticles (SPIONs), which are widely used as a robust T₂‐weighted, negative contrast agent on conventional MR images. Our study was designed (a) to optimize the dual‐contrast MRI method using SPIONs and (b) to validate the feasibility of simultaneously evaluating the vascular morphology, blood volume and transvascular permeability using the dual‐contrast effect of SPIONs. All studies were conducted using 3 T MRI. According to numerical simulation, 0.15 mM was the optimal blood SPION concentration for visualizing the positive contrast effect using UTE MRI (T_E = 0.09 ms), and a flip angle of 40° could provide sufficient SPION‐induced enhancement and acceptable measurement noise for UTE MR angiography. A pharmacokinetic study showed that this concentration can be steadily maintained from 30 to 360 min after the injection of 29 mg/kg of SPIONs. An in vivo study using these settings displayed image quality and CNR of SPION‐enhanced UTE MR angiography (image quality score 3.5; CNR 146) comparable to those of the conventional, Gd‐enhanced method (image quality score 3.8; CNR 148) (p > 0.05). Using dual‐contrast MR images obtained from SPION‐enhanced UTE and conventional spin‐ and gradient‐echo methods, the transvascular permeability (water exchange index 1.76–1.77), cerebral blood volume (2.58–2.60%) and vessel caliber index (3.06–3.10) could be consistently quantified (coefficient of variation less than 9.6%; Bland–Altman 95% limits of agreement 0.886–1.111) and were similar to the literature values. Therefore, using the optimized setting of combined SPION‐based MRI techniques, the vascular morphology, blood volume and transvascular permeability can be comprehensively evaluated during a single session of MR examination. Copyright © 2015 John Wiley & Sons, Ltd.     

Sequence design and evaluation of the reproducibility of water‐selective diffusion‐weighted imaging of the breast at 3 T

Diffusion measurements derived from breast MRI can be adversely affected by unwanted signals from abundant fatty tissues if they are not suppressed adequately. To minimize this undesired contribution, we designed and optimized a water‐selective diffusion‐weighted imaging (DWI) sequence, which relies on spectrally selective excitation on the water resonance, obviating the need for fat suppression. As this method is more complex than standard DWI methods, we also report a test–retest study to evaluate its reproducibility. In this study, a spectrally selective Gaussian pulse on water resonance was combined with a pair of slice‐selective adiabatic refocusing pulses for water‐only DWI. Field map‐based shimming and manual determination of the center frequency were used for water selection. The selectivity of the excitation pulse was optimized by a spectrally selective spectroscopy sequence based on the same principles. A test–retest study of 10 volunteers in two separate visits was used to evaluate its reproducibility. Our results from all subjects showed high‐quality diffusion‐weighted images of the breast without fat contamination. Mean apparent diffusion coefficients for b = 0, 600 s/mm² and b = 50, 600 s/mm² all showed good reproducibility, as 95% confidence intervals of the apparent diffusion coefficients were 4 × 10^–5 mm²/s and 5 × 10^–5 mm²/s and repeatability values were 1.09 × 10^–4 and 1.31 × 10^–4, respectively. In conclusion, water‐selective DWI is a feasible alternative to standard methods of DWI based on fat suppression. The added complexity of the method does not compromise the reproducibility of diffusion measurements in the breast. Copyright © 2014 John Wiley & Sons, Ltd.     

Metastatic melanoma volume in sentinel nodes: objective stereology-based measurement predicts disease recurrence and survival

Aims:  Sentinel lymph node (SLN) status is the most important prognostic factor in intermediate thickness melanoma. The amount of metastatic disease in positive SLNs varies greatly between patients, and this tumour burden appears to influence the prognosis of node-positive patients. The aim was to use objective stereological techniques to correlate accurately total SLN tumour burden with recurrence and patient survival.
Methods and results:  SLNs from 327 patients were examined by complete step sectioning and immunohistochemistry. The total metastasis volume (TMV) of 156 positive SLNs from 99 patients (30.3%) was measured using stereological methods based on the 2D-nucleator and Cavalieri's principle. The maximum metastasis diameter was also measured. These two measurements were correlated with disease recurrence and patient survival. The mean TMV for SLN+ patients was 10.5 mm³ (median 0.05 mm³; range 0.0001–623.7 mm³). Median follow-up was 26.3 months. On multivariate analysis, TMV was an independent predictor of recurrence when corrected for primary tumour thickness ( P  = 0.001) and was a stronger prognosticator compared with the maximum metastasis diameter ( P  < 0.0001 versus P  = 0.01).
Conclusions:  Combining total step sectioning of SLNs with stereological assessment of metastases, we found metastasis volume to be a highly significant predictor of disease recurrence and survival.     

Trochlear boss height measurement: A comparison of radiographs and MRI

BackgroundA key anatomical consideration and determinant of surgical approach in trochlear dysplasia is the trochlear boss height (TBH), traditionally defined by measurements on plain X-rays (XR). Magnetic resonance (MR) imaging is increasingly used for pre-operative planning and follow-up. However, it is unclear whether measurement of TBH on XR is applicable to MR. The aim of this study was to establish the reliability of TBH measurement on MR compared to XR.MethodsThis study used lateral knee radiographs and MR scans of 14 knees of patients with trochlear dysplasia, six knees of non-dysplastic patients with anterior knee pain (AKP), and five knees of non-dysplastic controls with no AKP. Correlation between XR and MR measurements was assessed using Pearson correlation coefficients. Agreement between methods and observers was assessed using Bland–Altman plots with 95% limits of agreement. Intra- and inter-observer reliability was assessed using intraclass correlation coefficients (ICC).ResultsBland–Altman charts showed a total width of 95% limits of agreement of 4.78 mm for XR and MR subchondral bone (SB) TBH measurements, and 6.73 mm for XR and MR cartilage TBH measurements. Inter-observer ICCs were 0.86 for XR, 0.62 for MR SB, and 0.53 for MR cartilage. The widths of the Bland–Altman 95% limits of agreement between observers were 4.79 mm (XR), 5.04 mm (MR SB) and 4.74 mm (MR cartilage).ConclusionMeasurement of TBH on MR is not directly interchangeable with XR. Adjustments need to be made to treatment thresholds based on XR measurement if MR is used instead.     

High resolution MRI evaluation of meniscal volume and anthropometric correlations

The purpose of this study was to digitally determine meniscal volumes, and compare them with linear and surface area anthropometric measurements to evaluate these measurements for meniscal allograft sizing. Eighteen subjects (10 male and 8 female; mean age 37.5 years) underwent 3.0 T knee magnetic resonance imaging (MRI) of the dominant leg. The following morphometric measurements were evaluated: medial meniscal volume (MMV), lateral meniscal volume (LMV), tibial plateau width (TPW), width of the femoral condyles (WFC), and tibial plateau surface area (TPSA). MMV and LMV were compared to TPW, WFC, and TPSA. Meniscal volume and TPW were correlated to height and body‐mass index (BMI) and stratified by gender. Statistical analysis included coefficient of determination (r²) between MRI‐based MMV, LMV, TPW, TPSA, WFC, height, BMI, and gender. Significance was set at the P = 0.05 level. The mean MMV was 2275 mm³ and the mean LMV was 2102 mm³. TPW correlated well with meniscal volumes (r² > 0.62). WFC and TPSA correlated with meniscal volumes in the range of 0.40 < r² < 0.61. Height, BMI, and gender correlated poorly with total meniscal volume and TPW with values of r² < 0.44. Medial and lateral menisci have statistically similar volumes. TPW had the greatest utility for volumetric meniscal sizing. MRI‐based TPW can be considered as a statistically accurate measurement for determining meniscal volumes and meniscal size. Clin. Anat. 28:786–791, 2015. © 2015 Wiley Periodicals, Inc.     

Clinical and pathological features of metastases of primary cutaneous desmoplastic melanoma

Murali R, Zannino D, Synnott M, McCarthy S W, Thompson J F & Scolyer R A
(2011) Histopathology  58 , 886–895
Clinical and pathological features of metastases of primary cutaneous desmoplastic melanoma Aims: Primary cutaneous desmoplastic melanoma (DM) may be entirely desmoplastic [‘pure’ DM (pDM)] or exhibit a desmoplastic component admixed with a non‐desmoplastic component [‘combined’ DM (cDM)]. Our aim was to describe the histological features of metastases of primary DM and to determine whether they were predictive of outcome. Methods: The effect of clinicopathological parameters on overall survival (OS) was analysed, and the correlation between histological features of the primary melanoma and metastases was studied in patients with metastatic DM. Results: Twenty‐six patients (18 males; eight females) developed 50 metastases in sentinel nodes (13; 26.0%), regional nodes (10; 20.0%), skin (14; 28.0%), and distant sites (13; 26.0%). The cellular composition of metastases correlated with that of the corresponding primary tumours. Time to development of first non‐sentinel lymph node metastasis was shorter in cDM than in pDM (median 11.2 versus 24.9 months, P = 0.075). The only independent predictors of poorer OS were cDM type [hazard ratio 6.17, 95% confidence interval (CI) 1.61–23.81, P = 0.008] and male sex (hazard ratio 5.98, 95% CI 1.34–26.66, P = 0.019). Conclusions: The cellular composition of primary DM correlates with that of metastatic DM and with outcome. It is important to consider the possibility of primary or metastatic DM when examining tumours composed of spindle cells.     

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.     

Comparison of capillary based microflurometric assay for CD4+ T cell count estimation with dual platform Flow cytometry

The CD4+ T cell count estimation is an important monitoring tool for HIV disease progression and efficacy of anti-retroviral treatment (ART). Due to availability of ART at low cost in developing countries, quest for reliable cost effective alternative methods for CD4+ T cell count estimation has gained importance. A simple capillary-based microflurometric assay (EasyCD4 System, Guava Technology) was compared with the conventional flow cytometric assay for estimation of CD4+ T cell counts in 79 HIV infected individuals. CD4+ T cell count estimation by both the assays showed strong correlation (r = 0.938, p < 0.001, 95% CI 0.90 to 0.96). The Bland Altman plot analysis showed that the limits of variation were within agreeable limits of ± 2SD (-161 to 129 cells/mm³). The Easy CD4 assay showed 100% sensitivity for estimating the CD4+ T cell counts < 200 cells/mm³ and < 350 cells/mm³ and 97% sensitivity to estimate CD4+ T cell count < 500 cells/mm³. The specificity ranged from 82 to 100%. The Kappa factor ranged from 0.735 for the CD4+ T cell counts < 350 cells/mm³ to 0.771 for < 500 cells/mm³ CD4+ T cell counts. The system works with a simple protocol, is easy to maintain and has low running cost. The system is compact and generates minimum amount of waste. Hence the EasyCD4 System could be applied for estimation of CD4+ T cell counts in resource poor settings.     

Considerations for measuring the fractional anisotropy of metabolites with diffusion tensor spectroscopy

Diffusion tensor spectroscopy of metabolites in brain is challenging because of their lower diffusivity (i.e. less signal attenuation for a given b value) and much poorer signal‐to‐noise ratio relative to water. Although diffusion tensor acquisition protocols have been studied in detail for water, they have not been evaluated systematically for the measurement of the fractional anisotropy of metabolites such as N‐acetylaspartate, creatine and choline in the white and gray matter of human brain. Diffusion tensor spectroscopy was performed in vivo with variable maximal b values (1815 or 5018 s/mm²). Experiments were also performed on simulated spectra and isotropic alcohol phantoms of various diffusivities, ranging from approximately 0.54 × 10^?3 to 0.13 × 10^?3 mm²/s, to assess the sensitivity of diffusion tensor spectroscopic parameters to low diffusivity, noise and b value. The low maximum b value of 1815 s/mm² yielded elevated fractional anisotropy (0.53–0.60) of N‐acetylaspartate in cortical gray matter relative to the more isotropic value (0.25–0.30) obtained with a higher b value of 5018 s/mm²; in contrast, the fractional anisotropy of white matter was consistently anisotropic with the different maximal b values (i.e. 0.43–0.54 for b = 1815 s/mm² and 0.47–0.51 for b = 5018 s/mm²). Simulations, phantoms and in vivo data indicate that greater signal attenuation, to a degree, is desirable for the accurate quantification of diffusion‐weighted spectra for slowly diffusing metabolites. Copyright © 2010 John Wiley & Sons, Ltd.