Quantitative myelin imaging with MRI and PET: an overview of techniques and their validation status.

Myelin is the protective sheath wrapped around axons, consisting of a phospholipid bilayer with water between the wraps. The measurement of damage to the myelin sheaths, the evaluation of the efficacy of therapies aiming to promote remyelination and monitoring the degree of brain maturation in children all require non-invasive quantitative myelin imaging methods. To date, various myelin imaging techniques have been developed. Five different MRI approaches can be distinguished based on their biophysical principles: (i) imaging of the water between the lipid bilayers directly (e.g. myelin water imaging); (ii) imaging the non-aqueous protons of the phospholipid bilayer directly with ultra-short echo-time techniques; (iii) indirect imaging of the macromolecular content (e.g. magnetization transfer; inhomogeneous magnetization transfer); (iv) mapping of the effects of the myelin sheath's magnetic susceptibility on the MRI signal (e.g. quantitative susceptibility mapping); and (v) mapping of the effects of the myelin sheath on water diffusion. Myelin imaging with PET uses radioactive molecules with high affinity to specific myelin components, in particular myelin basic protein. This review aims to give an overview of the various myelin imaging techniques, their biophysical principles, image acquisition, data analysis and their validation status.

Comparison of conventional and higher-resolution reduced-FOV diffusion-weighted imaging of breast tissue.

OBJECTIVE: Reduced FOV-diffusion-weighted imaging (rFOV-DWI) allows for acquisition of a tissue region without back-folding, and may have better fat suppression than conventional DWI imaging (c-DWI). The aim was to compare the ADCs obtained with c-DWI bilateral-breast imaging with single-breast rFOV-DWI. MATERIALS AND METHODS: Breasts of 38 patients were scanned at 3 T. The mean ADC values obtained for 38 lesions, and fibro-glandular (N = 35) and adipose (N = 38) tissue ROIs were compared between c-DWI and higher-resolution rFOV-DWI (Wilcoxon rank test). Also, the ADCs were compared between the two acquisitions for an oil-only phantom and a combined water/oil phantom. Furthermore, ghost artifacts were assessed. RESULTS: No significant difference in mean ADC was found between the acquisitions for lesions (c-DWI: 1.08 × 10-3 mm2/s, rFOV-DWI: 1.13 × 10-3 mm2/s) and fibro-glandular tissue. For adipose tissue, the ADC using rFOV-DWI (0.31 × 10-3 mm2/s) was significantly higher than c-DWI (0.16 × 10-3 mm2/s). For the oil-only phantom, no difference in ADC was found. However, for the water/oil phantom, the ADC of oil was significantly higher with rFOV-DWI compared to c-DWI. DISCUSSION: Although ghost artifacts were observed for both acquisitions, they appeared to have a greater impact for rFOV-DWI. However, no differences in mean lesions' ADC values were found, and therefore this study suggests that rFOV can be used diagnostically for single-breast DWI imaging.

Early imaging biomarkers of lung cancer, COPD and coronary artery disease in the general population: rationale and design of the ImaLife (Imaging in Lifelines) Study.

Lung cancer, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD) are expected to cause most deaths by 2050. State-of-the-art computed tomography (CT) allows early detection of lung cancer and simultaneous evaluation of imaging biomarkers for the early stages of COPD, based on pulmonary density and bronchial wall thickness, and of CAD, based on the coronary artery calcium score (CACS), at low radiation dose. To determine cut-off values for positive tests for elevated risk and presence of disease is one of the major tasks before considering implementation of CT screening in a general population. The ImaLife (Imaging in Lifelines) study, embedded in the Lifelines study, is designed to establish the reference values of the imaging biomarkers for the big three diseases in a well-defined general population aged 45 years and older. In total, 12,000 participants will undergo CACS and chest acquisitions with latest CT technology. The estimated percentage of individuals with lung nodules needing further workup is around 1-2%. Given the around 10% prevalence of COPD and CAD in the general population, the expected number of COPD and CAD is around 1000 each. So far, nearly 4000 participants have been included. The ImaLife study will allow differentiation between normal aging of the pulmonary and cardiovascular system and early stages of the big three diseases based on low-dose CT imaging. This information can be finally integrated into personalized precision health strategies in the general population.

Quantitative DWI implemented after DCE-MRI yields increased specificity for BI-RADS 3 and 4 breast lesions.

PURPOSE: To assess if specificity can be increased when semiautomated breast lesion analysis of quantitative diffusion-weighted imaging (DWI) is implemented after dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) in the workup of BI-RADS 3 and 4 breast lesions larger than 1 cm. MATERIALS AND METHODS: In all, 120 consecutive patients (mean-age, 48 years; age range, 23-75 years) with 139 breast lesions (≥1 cm) were examined (2010-2014) with 1.5T DCE-MRI and DWI (b = 0, 50, 200, 500, 800, 1000 s/mm2 ) and the BI-RADS classification and histopathology were obtained. For each lesion malignancy was excluded using voxelwise semiautomated breast lesion analysis based on previously defined thresholds for the apparent diffusion coefficient (ADC) and the three intravoxel incoherent motion (IVIM) parameters: molecular diffusion (Dslow ), microperfusion (Dfast ), and the fraction of Dfast (ffast ). The sensitivity (Se), specificity (Sp), and negative predictive value (NPV) based on only IVIM parameters combined in parallel (Dslow , Dfast , and ffast ), or the ADC or the BI-RADS classification by DCE-MRI were compared. Subsequently, the Se, Sp, and NPV of the combination of the BI-RADS classification by DCE-MRI followed by the IVIM parameters in parallel (or the ADC) were compared. RESULTS: In all, 23 of 139 breast lesions were benign. Se and Sp of DCE-MRI was 100% and 30.4% (NPV = 100%). Se and Sp of IVIM parameters in parallel were 92.2% and 52.2% (NPV = 57.1%) and for the ADC 95.7% and 17.4%, respectively (NPV = 44.4%). In all, 26 of 139 lesions were classified as BI-RADS 3 (n = 7) or BI-RADS 4 (n = 19). DCE-MRI combined with ADC (Se = 99.1%, Sp = 34.8%) or IVIM (Se = 99.1%, Sp = 56.5%) did significantly improve (P = 0.016) Sp of DCE-MRI alone for workup of BI-RADS 3 and 4 lesions (NPV = 92.9%). CONCLUSION: Quantitative DWI has a lower NPV compared to DCE-MRI for evaluation of breast lesions and may therefore not be able to replace DCE-MRI; when implemented after DCE-MRI as problem solver for BI-RADS 3 and 4 lesions, the combined specificity improves significantly. J. Magn. Reson. Imaging 2016;44:1642-1649.

Semi-automated quantitative intravoxel incoherent motion analysis and its implementation in breast diffusion-weighted imaging.

BACKGROUND: To optimize and validate intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) compared with the apparent diffusion coefficient (ADC) for semi-automated analysis of breast lesions using a multi-reader setup. MATERIALS AND METHODS: Patients (n = 176) with breast lesions (≥1 cm) and known pathology were prospectively examined (1.5 Tesla) with DWI (b = 0, 50, 200, 500, 800, 1000 s/mm(2) ) between November 2008 and July 2014 and grouped into a training and test set. Three independent readers applied a semi-automated procedure for setting regions-of-interest for each lesion and recorded ADC and IVIM parameters: molecular diffusion (Dslow ), microperfusion (Dfast ), and the fraction of Dfast (ffast ). In the training set (24 lesions, 12 benign), a semi-automated method was optimized to yield maximum true negatives (TN) with minimal false negatives (FN): only the optimal fraction (Fo) of voxels in the lesions was used and optimal thresholds were determined. The optimal Fo and thresholds were then applied to a consecutive test set (139 lesions, 23 benign) to obtain specificity and sensitivity. RESULTS: In the training set, optimal thresholds were 1.44 × 10(-3) mm(2) /s (Dslow ), 18.55 × 10(-3) mm(2) /s (Dfast ), 0.247 (ffast ) and 2.00 × 10(-3) mm(2) /s (ADC) with Fo set to 0.61, 0.85, 1.0, and 1.0, respectively, this resulted in TN = 5 (IVIM) and TN = 1 (ADC), with FN = 0. In the test set, sensitivity and specificity among the readers were 90.5-93.1% and 43.5-52.2%, respectively, for IVIM, and 94.8-95.7% and 13.0-21.7% for ADC (P ≤ 0.0034) without inter-reader differences (P = 1.000). CONCLUSION: The presented semi-automated method for breast lesion evaluation is reader independent and yields significantly higher specificity for IVIM compared with the ADC.

Contrast-optimized composite image derived from multigradient echo cardiac magnetic resonance imaging improves reproducibility of myocardial contours and T2* measurement.

OBJECTIVES: Reproducibility of myocardial contour determination in cardiac magnetic resonance imaging is important, especially when determining T2* values per myocardial segment as a prognostic factor of heart failure or thalassemia. A method creating a composite image with contrasts optimized for drawing myocardial contours is introduced and compared with the standard method on a single image. MATERIALS AND METHODS: A total of 36 short-axis slices from bright-blood multigradient echo (MGE) T2* scans of 21 patients were acquired at eight echo times. Four observers drew free-hand myocardial contours on one manually selected T2* image (method 1) and on one image composed by blending three images acquired at TEs providing optimum contrast-to-noise ratio between the myocardium and its surrounding regions (method 2). RESULTS: Myocardial contouring by method 2 met higher interobserver reproducibility than method 1 (P < 0.001) with smaller Coefficient of variance (CoV) of T2* values in the presence of myocardial iron accumulation (9.79 vs. 15.91%) and in both global myocardial and mid-ventricular septum regions (12.29 vs. 16.88 and 5.76 vs. 8.16%, respectively). CONCLUSION: The use of contrast-optimized composite images in MGE data analysis improves reproducibility of myocardial contour determination, leading to increased consistency in the calculated T2* values enhancing the diagnostic impact of this measure of iron overload.

Effect of b value and pre-admission of contrast on diagnostic accuracy of 1.5-T breast DWI: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the effect of the choice of b values and prior use of contrast medium on apparent diffusion coefficients (ADCs) of breast lesions derived from diffusion-weighted imaging (DWI), and on the discrimination between benign and malignant lesions. METHODS: A literature search of relevant DWI studies was performed. The accuracy of DWI to characterize lesions by using b value ≤600 s/mm(2) and b value >600 s/mm(2) was presented as pooled sensitivity and specificity, and the ADC was calculated for both groups. Lesions were pooled as pre- or post-contrast DWI. RESULTS: Of 198 articles, 26 met the inclusion criteria. Median ADCs were significantly higher (13.2-35.1 %, p < 0.001) for the group of b values ≤600 s/mm(2) compared to >600 s/mm(2). The sensitivity in both groups was similar (91 % and 89 %, p = 0.495) as well as the specificity (75 % and 84 %, p = 0.237). Contrast medium had no significant effects on the ADCs (p ≥ 0.08). The differentiation between benign and malignant lesions was optimal (58.4 %) for the combination of b = 0 and 1,000 s/mm(2). CONCLUSIONS: The wide variety of b value combinations applied in different studies significantly affects the ADC of breast lesions and confounds quantitative DWI. If only a couple of b values are used, those of b = 0 and 1,000 s/mm(2) are recommended for the best improvement of differentiating between benign and malignant lesions. KEY POINTS: • The choice of b values significantly affects the ADC of breast lesions. • Sensitivity and specificity are not affected by the choice of b values. • b values 0 and 1,000 s/mm (2) are recommended for optimal differentiation between benign and malignant lesions. • Contrast medium prior to DWI does not significantly affect the ADC.

Effects of microperfusion in hepatic diffusion weighted imaging.

OBJECTIVE: Clinical hepatic diffusion weighted imaging (DWI) generally relies on mono-exponential diffusion. The aim was to demonstrate that mono-exponential diffusion in the liver is contaminated by microperfusion and that the bi-exponential model is required. METHODS: Nineteen fasting healthy volunteers were examined with DWI (seven b-values) using fat suppression and respiratory triggering (1.5 T). Five different regions in the liver were analysed regarding the mono-exponentially fitted apparent diffusion coefficient (ADC), and the bi-exponential model: molecular diffusion (D (slow)), microperfusion (D (fast)) and the respective fractions (f (slow/fast)). Data were compared using ANOVA and Kruskal-Wallis tests. Simulations were performed by repeating our data analyses, using just the DWI series acquired with b-values approximating those of previous studies. RESULTS: Median mono-exponentially fitted ADCs varied significantly (P < 0.001) between 1.107 and 1.423 × 10(-3) mm(2)/s for the five regions. Bi-exponential fitted D(slow) varied between 0.923 and 1.062 × 10(-3) mm(2)/s without significant differences (P = 0.140). D (fast) varied significantly, between 17.8 and 46.8 × 10(-3) mm(2)/s (P < 0.001). F-tests showed that the diffusion data fitted the bi-exponential model significantly better than the mono-exponential model (F > 21.4, P < 0.010). These results were confirmed by the simulations. CONCLUSION: ADCs of normal liver tissue are significantly dependent on the measurement location because of substantial microperfusion contamination; therefore the bi-exponential model should be used. KEY POINTS: Diffusion weighted MR imaging helps clinicians to differentiate tumours by diffusion properties. Fast moving water molecules experience microperfusion, slow molecules diffusion. Hepatic diffusion should be measured by bi-exponential models to avoid microperfusion contamination. Mono-exponential models are contaminated with microperfusion, resulting in apparent regional diffusion differences. Bi-exponential models are necessary to measure diffusion and microperfusion in the liver.

Quantitative and qualitative assessment of structural magnetic resonance imaging data in a two-center study.

BACKGROUND: Multi-center magnetic resonance imaging (MRI) studies present an opportunity to advance research by pooling data. However, brain measurements derived from MR-images are susceptible to differences in MR-sequence parameters. It is therefore necessary to determine whether there is an interaction between the sequence parameters and the effect of interest, and to minimise any such interaction by careful choice of acquisition parameters. As an exemplar of the issues involved in multi-center studies, we present data from a study in which we aimed to optimize a set of volumetric MRI-protocols to define a protocol giving data that are consistent and reproducible across two centers and over time. METHODS: Optimization was achieved based on data quality and quantitative measures, in our case using FreeSurfer and Voxel Based Morphometry approaches. Our approach consisted of a series of five comparisons. Firstly, a single-center dataset was collected, using a range of candidate pulse-sequences and parameters chosen on the basis of previous literature. Based on initial results, a number of minor changes were implemented to optimize the pulse-sequences, and a second single-center dataset was collected. FreeSurfer data quality measures were compared between datasets in order to determine the best performing sequence(s), which were taken forward to the next stage of testing. We subsequently acquired short-term and long-term two-center reproducibility data, and quantitative measures were again assessed to determine the protocol with the highest reproducibility across centers. Effects of a scanner software and hardware upgrade on the reproducibility of the protocols at one of the centers were also evaluated. RESULTS: Assessing the quality measures from the first two datasets allowed us to define artefact-free protocols, all with high image quality as assessed by FreeSurfer. Comparing the quantitative test and retest measures, we found high within-center reproducibility for all protocols, but lower between-center reproducibility for some protocols than others. The upgrade showed no important effects. CONCLUSIONS: We were able to determine (for the scanners used in this study) an optimised protocol, which gave the highest within- and between-center reproducibility of those assessed, and give details of this protocol here. More generally, we discuss some of the issues raised by multi-center studies and describe a methodical approach to take towards optimization and standardization, and recommend performing this kind of procedure to other investigators.

Introduction of the Grayscale Median for Ultrasound Tissue Characterization of the Transplanted Kidney.

Ultrasound examination is advised for early post-kidney transplant assessment. Grayscale median (GSM) quantification is novel in the kidney transplant field, with no systematic assessment previously reported. In this prospective cohort study, we measured the post-operative GSM in a large cohort of adult kidney transplant recipients (KTR) who consecutively underwent Doppler ultrasound directly after transplantation (within 24 h), compared it with GSM in nontransplanted patients, and investigated its association with baseline and follow-up characteristics. B-mode images were used to calculate the GSM in KTR and compared with GSM data in nontransplanted patients, as simulated from summary statistics of the literature using a Mersenne twister algorithm. The association of GSM with baseline and 1-year follow-up characteristics were studied by means of linear regression analyses. In 282 KTR (54 ± 15 years old, 60% male), the median (IQR) GSM was 55 (45-69), ranging from 22 to 124 (coefficient of variation = 7.4%), without differences by type of donation (p = 0.28). GSM in KTR was significantly higher than in nontransplanted patients (p < 0.001), and associated with systolic blood pressure, history of cardiovascular disease, and donor age (std. ß = 0.12, -0.20, and 0.13, respectively; p < 0.05 for all). Higher early post-kidney transplant GSM was not associated with 1-year post-kidney transplant function parameters (e.g., measured and estimated glomerular filtration rate). The data provided in this study could be used as first step for further research on the application of early postoperative ultrasound in KTR.

Which patients are prone to undergo disproportionate recurrent CT imaging and should we worry?

PURPOSE: To identify the spectrum of patients who undergo disproportionate recurrent computed tomography (CT) imaging, and to explore the cumulative effects of radiation exposure and intravenously injected contrast agents in these patients. METHODS: This retrospective study investigated all patients who had undergone 40 or more CT scans at a tertiary care center between 2007-2017. RESULTS: Fifty-six patients who had undergone a median of 47 (range: 40-92) CT scans were included. The main reason for CT scanning in all patients was oncological, and 55 patients (98.2 %) had metastatic disease. Twenty-six patients (45.6) had received chemotherapy, 35 (62.5 %) radiation therapy, 38 (67.9 %) targeted therapy, 12 (21.4 %) liver tumor microwave ablation, 44 (78.6 %) major surgery, and 34 (60.7 %) had participated in a therapeutic trial. Mean cumulative effective dose was 187.4 mSv (range: 120.7-278.4 mSv). Median estimated radiation-induced lifetime attributable risk (LAR) of cancer incidence was 1.0 % (range: 0.20-2.36 %). Mean estimated radiation-induced LAR of cancer mortality was 0.68 % (range: 0.18-1.37 %). Mean cumulative volume of intravenously injected iomeprol was 2339 mL (range: 540-3605 mL). Three patients (5.4 %) had developed severely decreased kidney function (estimated glomerular filtration rate between 15 and 29 mL/min per 1.73 m² for at least 3 months). CONCLUSION: Patients with metastatic disease who experience a relatively long survival may be prone to undergo disproportionate recurrent CT imaging. The non-negligible CT radiation-induced cancer risk and mortality should be taken into account in these patients, while the effect of cumulatively administered CT contrast agents on kidney function requires further investigation.

Optimisation of three-dimensional lower jaw resection margin planning using a novel Black Bone magnetic resonance imaging protocol.

BACKGROUND: MRI is the optimal method for sensitive detection of tumour tissue and pre-operative staging in oral cancer. When jawbone resections are necessary, the current standard of care for oral tumour surgery in our hospital is 3D virtual planning from CT data. 3D printed jawbone cutting guides are designed from the CT data. The tumour margins are difficult to visualise on CT, whereas they are clearly visible on MRI scans. The aim of this study was to change the conventional CT-based workflow by developing a method for 3D MRI-based lower jaw models. The MRI-based visualisation of the tumour aids in planning bone resection margins. MATERIALS AND FINDINGS: A workflow for MRI-based 3D surgical planning with bone cutting guides was developed using a four-step approach. Key MRI parameters were defined (phase 1), followed by an application of selected Black Bone MRI sequences on healthy volunteers (phase 2). Three Black Bone MRI sequences were chosen for phase 3: standard, fat saturated, and an out of phase sequence. These protocols were validated by applying them on patients (n = 10) and comparison to corresponding CT data. The mean deviation values between the MRI- and the CT-based models were 0.63, 0.59 and 0.80 mm for the three evaluated Black Bone MRI sequences. Phase 4 entailed examination of the clinical value during surgery, using excellently fitting printed bone cutting guides designed from MRI-based lower jaw models, in two patients with oral cancer. The mean deviation of the resection planes was 2.3 mm, 3.8 mm for the fibula segments, and the mean axis deviation was the fibula segments of 1.9°. CONCLUSIONS: This study offers a method for 3D virtual resection planning and surgery using cutting guides based solely on MRI imaging. Therefore, no additional CT data are required for 3D virtual planning in oral cancer surgery.

Assessment of the link between quantitative biexponential diffusion-weighted imaging and contrast-enhanced MRI in the liver.

PURPOSE: To investigate if intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) can be linked to contrast-enhanced (CE-)MRI in liver parenchyma and liver lesions. METHODS: Twenty-five patients underwent IVIM-DWI followed by multiphase CE-MRI using Gd-EOB-DTPA (n=20) or Gd-DOTA (n=5) concluded with IVIM-DWI. Diffusion (Dslow), microperfusion (Dfast), its fraction (ffast), wash-in-rate (Rearly) and late-enhancement-rate (Rlate) of Gd-EOB-DTPA were calculated voxel-wise for the liver. Parenchyma and lesions were segmented. Pre-contrast IVIM was compared 1) between low, medium and high Rearly for parenchyma 2) to post-contrast IVIM substantiated with simulations 3) between low and high Rlate per lesion type. RESULTS: Dfast and ffast increased (P<0.001) with 25.6% and 33.8% between low and high Rearly of Gd-EOB-DTPA. Dslow decreased (-15.0%; P<0.001) with increasing Rearly. Gd-DOTA demonstrated similar observations. ffast (+10%; P<0.001) and Dfast (+6.6%; P<0.001) increased after Gd-EOB-DTPA, while decreasing after Gd-DOTA (-4.2% and -5.7%, P<0.001) and were confirmed by simulations. For focal nodular hyperplasia lesions (n=5) Dfast and ffast increased (P<0.001) with increasing Rlate, whereas for hepatocellular carcinoma (n=4) and adenoma (n=7) no differences were found. CONCLUSION: Microperfusion measured by IVIM reflects perfusion in a way resembling CE-MRI. Also IVIM separated intra- and extracellular MR contrast media. This underlines the potential of IVIM in quantitative liver imaging.

Diminished liver microperfusion in Fontan patients: A biexponential DWI study.

It has been demonstrated that hepatic apparent diffusion coefficients (ADC) are decreasing in patients with a Fontan circulation. It remains however unclear whether this is a true decrease of molecular diffusion, or rather reflects decreased microperfusion due to decreased portal blood flow. The purpose of this study was therefore to differentiate diffusion and microperfusion using intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) for different liver segments in patients with a Fontan circulation, compare to a control group, and relate with liver function, chronic hepatic congestion and hepatic disease. For that purpose, livers of 59 consecutively included patients with Fontan circulation (29 men; mean-age, 19.1 years) were examined (Oct 2012─Dec 2013) with 1.5T MRI and DWI (b = 0,50,100,250,500,750,1500,1750 s/mm2). IVIM (Dslow, Dfast, ffast) and ADC were calculated for eight liver segments, compared to a control group (19 volunteers; 10 men; mean-age, 32.9 years), and correlated to follow-up duration, clinical variables, and laboratory measurements associated with liver function. The results demonstrated that microperfusion was reduced (p<0.001) in Fontan livers compared to controls with ─38.1% for Dfast and ─32.6% for ffast. Molecular diffusion (Dslow) was similar between patients and controls, while ADC was significantly lower (─14.3%) in patients (p<0.001). ADC decreased significantly with follow-up duration after Fontan operation (r = ─0.657). Dslow showed significant inverse correlations (r = ─0.591) with follow-up duration whereas Dfast and ffast did not. From these results it was concluded that the decreasing ADC values in Fontan livers compared with controls reflect decreases in hepatic microperfusion rather than any change in molecular diffusion. However, with the time elapsed since the Fontan operation molecular diffusion and ADC decreased while microperfusion remained stable. This indicates that after Fontan operation initial blood flow effects on the liver are followed by intracellular changes preceding the formation of fibrosis and cirrhosis.

The Fontan circulation and the liver: A magnetic resonance diffusion-weighted imaging study.

BACKGROUND: Patients with a Fontan circulation tend to develop liver fibrosis, liver cirrhosis and even hepatocellular carcinoma. The aim of this study is to use the magnetic resonance technique diffusing-weighted imaging (DWI) for detecting liver fibrosis/cirrhosis in Fontan patients and to establish whether DWI results are associated with functional aspects of the Fontan circulation. METHODS: In a cross-sectional study, 59 Fontan patients were evaluated by liver DWI. The association between apparent diffusion coefficients (ADC) and patient characteristics, laboratory measurements and functional aspects of the Fontan circulation (NYHA class, maximum oxygen uptake during exercise and cardiac index) was assessed. RESULTS: Liver ADC values were low (0.82×10(-3)±0.11×10(-3) mm2/s) compared with literature values for healthy volunteers and correlated negatively with calculated liver fibrosis/cirrhosis scores (Fib-4 score, p=0.019; AST/ALT ratio, p=0.009) and gamma-glutamyl transferase (p=0.001). Furthermore, ADC values correlated negatively with follow-up duration (p<0.001) and positively with cardiac index (p=0.019). No correlation between ADC values and exercise tests was found. In multivariable analysis, the ADC values were independently correlated with follow-up duration after Fontan completion. CONCLUSIONS: The results of the current study suggest that progressive liver damage due to chronic congestion and potential hypoperfusion is reflected in the liver ADC values in Fontan patients. This study highlights that liver damage in the context of the Fontan circulation might be far more common than previously thought, and that the implementation of liver assessment in the routine follow-up of Fontan patients is recommendable.

Intermodel agreement of myocardial blood flow estimation from stress-rest myocardial perfusion magnetic resonance imaging in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to assess the intermodel agreement of different magnetic resonance myocardial perfusion models and evaluate their correspondence to stenosis diameter. MATERIALS AND METHODS: In total, 260 myocardial segments were analyzed from rest and adenosine stress first-pass myocardial perfusion magnetic resonance images (1.5 T, 0.050 ± 0.005 mmol/kg body weight gadolinium; 122 segments in rest, 138 in stress) in 10 patients with suspected or known coronary artery disease. Signal intensity curves were calculated per myocardial segment, of which the contours were traced with QMASS MR V.7.6 (Medis, Leiden, the Netherlands), and exported to Matlab. Myocardial blood flow quantification was performed with distributed parameter, extended Toft, Patlak, and Fermi parametric models (in-house programs; Matlab R2013a; Mathworks Inc, Natick, MA). Modeling was applied after the signal intensity curves were corrected for spatial magnetic field inhomogeneity and contrast saturation. Overall and grouped perfusion values based on presence of coronary stenosis (>50% diameter reduction) at coronary computed tomography angiography at second generation dual-source computed tomography were compared between the perfusion models. RESULTS: Rest and stress myocardial perfusion estimates for all models were significantly related to each other (P < 0.001). The highest correlation coefficients were found between the extended Toft and Fermi models (R = 0.89-0.91) and low correlation coefficients between the distributed parameter and Patlak models (R = 0.66-0.68). The models resulted in significantly different perfusion estimates in stress (P = 0.03), but not in rest (P = 0.74). The differences in perfusion estimates in stress were caused by differences between the distributed parameter and Patlak models and between the Patlak and Fermi models (both P < 0.001). Significantly lower perfusion estimates were found for myocardial segments subtended by coronary arteries with versus without significant stenosis, but only for estimations produced by the extended Toft model (P = 0.04) and Fermi model (P = 0.01). There were no significant differences in rest perfusion values between models. CONCLUSIONS: Quantitative myocardial perfusion values in stress depend on the modeling method used to calculate the perfusion estimate. The difference in myocardial perfusion estimate with or without stenosis in the subtending coronary artery is most pronounced when the extended Toft or Fermi model is used.

Clinical implications of non-steatotic hepatic fat fractions on quantitative diffusion-weighted imaging of the liver.

Diffusion-weighted imaging (DWI) is an important diagnostic tool in the assessment of focal liver lesions and diffuse liver diseases such as cirrhosis and fibrosis. Quantitative DWI parameters such as molecular diffusion, microperfusion and their fractions, are known to be affected when hepatic fat fractions (HFF) are higher than 5.5% (steatosis). However, less is known about the effect on DWI for HFF in the normal non-steatotic range below 5.5%, which can be found in a large part of the population. The aim of this study was therefore to evaluate the diagnostic implications of non-steatotic HFF on quantitative DWI parameters in eight liver segments. For this purpose, eleven healthy volunteers (2 men, mean-age 31.0) were prospectively examined with DWI and three series of in-/out-of-phase dual-echo spoiled gradient-recalled MRI sequences to obtain the HFF and T2*. DWI data were analyzed using the intravoxel incoherent motion (IVIM) model. Four circular regions (ø22.3 mm) were drawn in each of eight liver segments and averaged. Measurements were divided in group 1 (HFF ≤ 2.75%), group 2 (2.75< HFF ≤ 5.5%) and group 3 (HFF>5.5%). DWI parameters and T2* were compared between the three groups and between the segments. It was observed that the molecular diffusion (0.85, 0.72 and 0.49 × 10(-3) mm(2)/s) and T2* (32.2, 27.2 and 21.0 ms) differed significantly between the three groups of increasing HFF (2.18, 3.50 and 19.91%). Microperfusion and its fraction remained similar for different HFF. Correlations with HFF were observed for the molecular diffusion (r = -0.514, p<0.001) and T2* (-0.714, p<0.001). Similar results were obtained for the majority of individual liver segments. It was concluded that fat significantly decreases molecular diffusion in the liver, also in absence of steatosis (HFF ≤ 5.5%). Also, it was confirmed that fat influences T2*. Determination of HFF prior to quantitative DWI is therefore crucial.

The cumulative risk of multiple CT exposures using two different methods.

The aim of this study was to compare the summing method (A) with the complement method (B) for calculating the cumulative lifetime-attributable-risk (LAR(tot)) of tumor incidence and mortality of multiple CT exposures. Method A defines LAR(tot) as the summation of the risk of each separate exposure. Method B was defined as the complement of the probability of inducing no cancer in N separate exposures. The risk of each separate exposure was estimated using dose, gender, and age at exposure (BEIR VII phase 2). Both methods were compared in a simulation and applied to a database of 11,884 patients exposed to multiple CTs. The relative difference between the methods was defined as ΔP%. Simulation confirmed that Method A always overestimates LAR(tot). ΔP% was proportional to the dose per exposure and the number of exposures. The differences between Methods A and B were small. Average LAR(tot) of tumor incidence was 0.140% (Method A) and 0.139% (Method B) with maxima of 5.70% and 5.56%, respectively. Average LAR(tot) of mortality was 0.085% for both methods, with maxima of 2.20% and 2.18%, respectively. ΔP% was highest (2.43%) for a female patient (3-y old) exposed to eight recurrent scans and a cumulative dose of 144 mSv. Although Method B is more accurate, both methods can be used to estimate the cumulative risk of multiple CT exposures. These results have to be interpreted, however, in the perspective of the uncertainties in the cancer risk model, which have been estimated at a factor of 2 or 3.

Coronary calcium mass scores measured by identical 64-slice MDCT scanners are comparable: a cardiac phantom study.

To assess whether absolute mass scores are comparable or differ between identical 64-slice MDCT scanners of the same manufacturer and to compare absolute mass scores to the physical mass and between scan modes using a calcified phantom. A non-moving anthropomorphic phantom with nine calcifications of three sizes and three densities was scanned 30 times on three 64-slice MDCT scanners of manufacturer A and on three 64-slice MDCT scanners of manufacturer B in both sequential and spiral scan mode. The mean mass scores and mass score variabilities of seven calcifications were determined for all scanners; two non-detectable calcifications were omitted. It was analyzed whether identical scanners yielded similar or significantly different mass scores. Furthermore mass scores were compared to the physical mass and mass scores were compared between scan modes. The mass score calibration factor was determined for all scanners. Mass scores obtained on identical scanners were similar for almost all calcifications. Overall, mass score differences between the scanners were small ranging from 1.5 to 3.4% for the total mass scores, and most differences between scanners were observed for high density calcifications. Mass scores were significantly different from the physical mass for almost all calcifications and all scanners. In sequential mode the total physical mass (167.8 mg) was significantly overestimated (+2.3%) for 4 out of 6 scanners. In spiral mode a significant overestimation (+2.5%) was found for system B and a significant underestimation (-1.8%) for two scanners of system A. Mass scores were dependent on the scan mode, for manufacturer A scores were higher in sequential mode and for manufacturer B in spiral mode. For system A using spiral scan mode no differences were found between identical scanners, whereas a few differences were found using sequential mode. For system B the scan mode did not affect the number of different mass scores between identical scanners. Mass scores obtained in the same scan mode are comparable between identical 64-slice CT scanners and identical 64-slice CT scanners on different sites can be used in follow-up studies. Furthermore, for all systems significant differences were found between mass scores and the physical calcium mass; however, the differences were relatively small and consistent.