Influence of saturation effects on biexponential liver intravoxel incoherent motion.

PURPOSE: Studies on intravoxel incoherent motion (IVIM) imaging in the liver have been carried out with different acquisition protocols. The number of acquired slices and the distances between slices can influence IVIM measurements due to saturation effects, but these effects have often been disregarded. This study investigated differences in biexponential IVIM parameters between two slice settings. METHODS: Fifteen healthy volunteers (21-30 years) were examined at a field strength of 3 T. Diffusion-weighted images of the abdomen were acquired with 16 b values (0-800 s/mm2 ), with four slices for the few slices setting and 24-27 slices for the many slices setting. Regions of interest were manually drawn in the liver. The data were fitted with a monoexponential signal curve and a biexponential IVIM curve, and biexponential IVIM parameters were determined. The dependence on the slice setting was assessed with Student's t test for paired samples (normally distributed IVIM parameters) and the Wilcoxon signed-rank test (non-normally distributed parameters). RESULTS: None of the parameters were significantly different between the settings. For few slices and many slices, respectively, the mean values (SDs) for D $$ D $$ were 1.21 µm 2 / ms $$ 1.21{\upmu \mathrm{m}}^2/\mathrm{ms} $$ ( 0.19 µm 2 / ms $$ 0.19\kern0.3em {\upmu \mathrm{m}}^2/\mathrm{ms} $$ ) and 1.20 µm 2 / ms $$ 1.20{\upmu \mathrm{m}}^2/\mathrm{ms} $$ ( 0.11 µm 2 / ms $$ 0.11\kern0.3em {\upmu \mathrm{m}}^2/\mathrm{ms} $$ ); for f $$ f $$ they were 29.7% (6.2%) and 27.7% (3.6%); and for D * $$ {D}^{\ast } $$ they were 8.76 ⋅ 10 - 2 mm 2 / s $$ 8.76\cdot {10}^{-2}{\mathrm{mm}}^2/\mathrm{s} $$ ( 4.54 ⋅ 10 - 2 mm 2 / s $$ 4.54\cdot {10}^{-2}\kern0.3em {\mathrm{mm}}^2/\mathrm{s} $$ ) and 8.71 ⋅ 10 - 2 mm 2 / s $$ 8.71\cdot {10}^{-2}{\mathrm{mm}}^2/\mathrm{s} $$ ( 4.06 ⋅ 10 - 2 mm 2 / s $$ 4.06\cdot {10}^{-2}\kern0.3em {\mathrm{mm}}^2/\mathrm{s} $$ ). CONCLUSION: Biexponential IVIM parameters in the liver are comparable among IVIM studies that use different slice settings, with mostly negligible saturation effects. However, this may not hold for studies that use much shorter TR.

Reduction of the cardiac pulsation artifact and improvement of lesion conspicuity in flow-compensated diffusion images in the liver-A quantitative evaluation of postprocessing algorithms.

PURPOSE: To enhance image quality of flow-compensated diffusion-weighted liver MRI data by increasing the lesion conspicuity and reducing the cardiac pulsation artifact using postprocessing algorithms. METHODS: Diffusion-weighted image data of 40 patients with liver lesions had been acquired at 1.5 T. These data were postprocessed with 5 different algorithms (weighted averaging, p-mean, percentile, outlier exclusion, and exception set). Four image properties of the postprocessed data were evaluated for optimizing the algorithm parameters. These properties were the lesion to tissue contrast-to-noise ratio (CNR), the reduction of the cardiac pulsation artifact, the data consistency, and the vessel darkness. They were combined into a total quality score ( Q total , $$ {Q}_{\mathrm{total}}, $$ set to 1 for the trace-weighted reference image), which was used to rate the image quality objectively. RESULTS: The weighted averaging algorithm performed best according to the total quality score ( Q total = 1.111 ± 0.067 $$ {Q}_{\mathrm{total}}=1.111\pm 0.067 $$ ). The further ranking was outlier exclusion algorithm ( Q total = 1.086 ± 0.061 $$ {Q}_{\mathrm{total}}=1.086\pm 0.061 $$ ), p-mean algorithm ( Q total = 1.045 ± 0.049 $$ {Q}_{\mathrm{total}}=1.045\pm 0.049 $$ ), percentile algorithm ( Q total = 1.012 ± 0.049 $$ {Q}_{\mathrm{total}}=1.012\pm 0.049 $$ ), and exception set algorithm ( Q total = 0.957 ± 0.027 $$ {Q}_{\mathrm{total}}=0.957\pm 0.027 $$ ). All optimized algorithms except for the exception set algorithm corrected the pulsation artifact and increased the lesion CNR. Changes in Q total $$ {Q}_{\mathrm{total}} $$ were significant for all optimized algorithms except for the percentile algorithm. Liver ADC was significantly reduced (except for the exception set algorithm), particularly in the left lobe. CONCLUSION: Postprocessing algorithms should be used for flow-compensated liver DWI. The proposed weighted averaging algorithm seems to be suited best to increase the image quality of artifact-corrupted flow-compensated diffusion-weighted liver data.

Echo time dependence of biexponential and triexponential intravoxel incoherent motion parameters in the liver.

PURPOSE: Intravoxel incoherent motion (IVIM) studies are performed with different acquisition protocols. Comparing them requires knowledge of echo time (TE) dependencies. The TE-dependence of the biexponential perfusion fraction f is well-documented, unlike that of its triexponential counterparts f1 and f2 and the biexponential and triexponential pseudodiffusion coefficients D* , D1∗ , and D2∗ . The purpose was to investigate the TE-dependence of these parameters and to check whether the triexponential pseudodiffusion compartments are associated with arterial and venous blood. METHODS: Fifteen healthy volunteers (19-58 y; mean: 24.7 y) underwent diffusion-weighted imaging of the abdomen with 24 b-values (0.2-800 s/mm2 ) at TEs of 45, 60, 75, and 90 ms. Regions of interest (ROIs) were manually drawn in the liver. One set of bi- and triexponential IVIM parameters per volunteer and TE was determined. The TE-dependence was assessed with the Kruskal-Wallis test. RESULTS: TE-dependence was observed for f (P < .001), f1 (P = .001), and f2 (P < .001). Their median values at the four measured TEs were: f: 0.198/0.240/0.274/0.359, f1 : 0.113/0.139/0.146/0.205, f2 : 0.115/0.155/0.182/0.194. D, D* , D1∗ , and D2∗ showed no significant TE-dependence. Their values were: diffusion coefficient D (10-4 mm2 /s): 9.45/9.63/9.75/9.41, biexponential D* (10-2 mm2 /s): 5.26/5.52/6.13/5.82, triexponential D1∗ (10-2 mm2 /s): 1.73/2.91/2.25/2.51, triexponential D2∗ (mm2 /s): 0.478/1.385/0.616/0.846. CONCLUSION: f1 and f2 show similar TE-dependence as f, ie, increase with rising TE; an effect that must be accounted for when comparing different studies. The diffusion and pseudodiffusion coefficients might be compared without TE correction. Because of the similar TE-dependence of f1 and f2 , the triexponential pseudodiffusion compartments are most probably not associated to venous and arterial blood.

Differentiating Benign and Malignant Breast Lesions in Diffusion Kurtosis MRI: Does the Averaging Procedure Matter?

BACKGROUND: Diffusion kurtosis imaging (DKI) is used to differentiate between benign and malignant breast lesions. DKI fits are performed either on voxel-by-voxel basis or using volume-averaged signal. PURPOSE: Investigate and compare DKI parameters' diagnostic performance using voxel-by-voxel and volume-averaged signal fit approach. STUDY TYPE: Retrospective. STUDY POPULATION: A total of 104 patients, aged 24.1-86.4 years. FIELD STRENGTH/SEQUENCE: A 3 T Spin-echo planar diffusion-weighted sequence with b-values: 50 s/mm2 , 750 s/mm2 , and 1500 s/mm2 . Dynamic contrast enhanced (DCE) sequence. ASSESSMENT: Lesions were manually segmented by M.P. under supervision of S.O. (2 and 5 years of experience in breast MRI). DKI fits were performed on voxel-by-voxel basis and with volume-averaged signal. Diagnostic performance of DKI parameters D K (kurtosis corrected diffusion coefficient) and kurtosis K was compared between both approaches. STATISTICAL TESTS: Receiver operating characteristics analysis and area under the curve (AUC) values were computed. Wilcoxon rank sum and Students t-test tested DKI parameters for significant (P <0.05) difference between benign and malignant lesions. DeLong test was used to test the DKI parameter performance for significant fit approach dependency. Correlation between parameters of the two approaches was determined by Pearson correlation coefficient. RESULTS: DKI parameters were significantly different between benign and malignant lesions for both fit approaches. Median benign vs. malignant values for voxel-by-voxel and volume-averaged approach were 2.00 vs. 1.28 ( D K in µm2 /msec), 2.03 vs. 1.26 ( D K in µm2 /msec), 0.54 vs. 0.90 ( K ), 0.55 vs. 0.99 ( K ). AUC for voxel-by-voxel and volume-averaged fit were 0.9494 and 0.9508 ( D K ); 0.9175 and 0.9298 ( K ). For both, AUC did not differ significantly (P = 0.20). Correlation of values between the two approaches was very high (r = 0.99 for D K and r = 0.97 for K ). DATA CONCLUSION: Voxel-by-voxel and volume-averaged signal fit approach are equally well suited for differentiating between benign and malignant breast lesions in DKI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Nonparametric D-R1-R2 distribution MRI of the living human brain.

Diffusion-relaxation correlation NMR can simultaneously characterize both the microstructure and the local chemical composition of complex samples that contain multiple populations of water. Recent developments on tensor-valued diffusion encoding and Monte Carlo inversion algorithms have made it possible to transfer diffusion-relaxation correlation NMR from small-bore scanners to clinical MRI systems. Initial studies on clinical MRI systems employed 5D D-R1 and D-R2 correlation to characterize healthy brain in vivo. However, these methods are subject to an inherent bias that originates from not including R2 or R1 in the analysis, respectively. This drawback can be remedied by extending the concept to 6D D-R1-R2 correlation. In this work, we present a sparse acquisition protocol that records all data necessary for in vivo 6D D-R1-R2 correlation MRI across 633 individual measurements within 25 min-a time frame comparable to previous lower-dimensional acquisition protocols. The data were processed with a Monte Carlo inversion algorithm to obtain nonparametric 6D D-R1-R2 distributions. We validated the reproducibility of the method in repeated measurements of healthy volunteers. For a post-therapy glioblastoma case featuring cysts, edema, and partially necrotic remains of tumor, we present representative single-voxel 6D distributions, parameter maps, and artificial contrasts over a wide range of diffusion-, R1-, and R2-weightings based on the rich information contained in the D-R1-R2 distributions.

Brain tissues have single-voxel signatures in multi-spectral MRI.

Since the seminal works by Brodmann and contemporaries, it is well-known that different brain regions exhibit unique cytoarchitectonic and myeloarchitectonic features. Transferring the approach of classifying brain tissues - and other tissues - based on their intrinsic features to the realm of magnetic resonance (MR) is a longstanding endeavor. In the 1990s, atlas-based segmentation replaced earlier multi-spectral classification approaches because of the large overlap between the class distributions. Here, we explored the feasibility of performing global brain classification based on intrinsic MR features, and used several technological advances: ultra-high field MRI, q-space trajectory diffusion imaging revealing voxel-intrinsic diffusion properties, chemical exchange saturation transfer and semi-solid magnetization transfer imaging as a marker of myelination and neurochemistry, and current neural network architectures to analyze the data. In particular, we used the raw image data as well to increase the number of input features. We found that a global brain classification of roughly 97 brain regions was feasible with gross classification accuracy of 60%; and that mapping from voxel-intrinsic MR data to the brain region to which the data belongs is possible. This indicates the presence of unique MR signals of different brain regions, similar to their cytoarchitectonic and myeloarchitectonic fingerprints.

Apparent exchange rate imaging: On its applicability and the connection to the real exchange rate.

PURPOSE: Water exchange between the intracellular and extracellular space can be measured using apparent exchange rate (AXR) imaging. The aim of this study was to investigate the relationship between the measured AXR and the geometry of diffusion restrictions, membrane permeability, and the real exchange rate, as well as to explore the applicability of AXR for typical human measurement settings. METHODS: The AXR measurements and the underlying exchange rates were simulated using the Monte Carlo method with different geometries, size distributions, packing densities, and a broad range of membrane permeabilities. Furthermore, the influence of SNR and sequence parameters was analyzed. RESULTS: The estimated AXR values correspond to the simulated values and show the expected proportionality to membrane permeability, except for fast exchange (ie, AXR>20-30s-1 ) and small packing densities. Moreover, it was found that the duration of the filter gradient must be shorter than 2·AXR-1 . In cell size and permeability distributions, AXR depends on the average surface-to-volume ratio, permeability, and the packing density. Finally, AXR can be reliably determined in the presence of orientation dispersion in axon-like structures with sufficient gradient sampling (ie, 30 gradient directions). CONCLUSION: Currently used experimental settings for in vivo human measurements are well suited for determining AXR, with the exception of single-voxel analysis, due to limited SNR. The detection of changes in membrane permeability in diseased tissue is nonetheless challenging because of the AXR dependence on further factors, such as packing density and geometry, which cannot be disentangled without further knowledge of the underlying cell structure.

An optimized b-value distribution for triexponential intravoxel incoherent motion (IVIM) in the liver.

PURPOSE: To find an optimized b-value distribution for reproducible triexponential intravoxel incoherent motion (IVIM) exams in the liver. METHODS: A numeric optimization of b-value distributions was performed using the triexponential IVIM equation and 27 different IVIM parameter sets. Starting with an initially optimized distribution of 6 b-values, the number of b-values was increased stepwise. Each new b-value was chosen from a set of 64 predefined b-values based on the computed summed relative mean error of the fitted triexponential IVIM parameters. This process was repeated for up to 100 b-values. In simulations and in vivo measurements, optimized b-value distributions were compared to 4 representative distributions found in literature. RESULTS: The first 16 optimized b-values were 0, 0.3, 0.3, 70, 200, 800, 70, 1, 3.5, 5, 70, 1.2, 6, 45, 1.5, and 60 in units of s/mm2 . Low b-values were much more frequent than high b-values. The optimized b-value distribution resulted in a higher fit stability compared to distributions used in literature in both, simulation and in vivo measurements. Using more than 6 b-values, ideally 16 or more, increased the fit stability considerably. CONCLUSION: Using optimized b-values, the fit uncertainty in triexponential IVIM can be largely reduced. Ideally, 16 or more b-values should be acquired.

Effect of compression garments on muscle perfusion in delayed-onset muscle soreness: A quantitative analysis using intravoxel incoherent motion MR perfusion imaging.

The aim of this prospective cohort study was to evaluate the effect of compression garments under resting conditions and after the induction of delayed-onset muscle soreness (DOMS) by MR perfusion imaging using intravoxel incoherent motion (IVIM). Magnetic resonance imaging of both lower legs of 16 volunteers was performed before and after standardized eccentric exercises that induced DOMS. A compression garment (21-22 mmHg) was worn during and for 6 h after exercise on one randomly selected leg. IVIM MR imaging, represented as total muscle perfusion D*f, perfusion fraction f and tissue diffusivity D, were compared between baseline and directly, 30 min, 6 h and 48 h after exhausting exercise with and without compression. Creatine kinase levels and T2-weighted images were acquired at baseline and after 48 h. DOMS was induced in the medial head of the gastrocnemius muscle (MGM) in all volunteers. Compression garments did not show any significant effect on IVIM perfusion parameters at any time point in the MGM or the tibialis anterior muscle (p > 0.05). Microvascular perfusion in the MGM increased significantly in both the compressed and noncompressed leg between baseline measurements and those taken directly after and 30 min after the exercise: the relative median f increased by 31.5% and 24.7% in the compressed and noncompressed leg, respectively, directly after the exercise compared with the baseline value. No significant change in tissue perfusion occurred 48 h after the induction of DOMS compared with baseline. It was concluded that compression garments (21-22 mmHg) do not alter microvascular muscle perfusion at rest, nor do they have any significant effect during the regeneration phase of DOMS. In DOMS, only a short-term effect of increased muscle perfusion (30 min after exercise) was observed, with normalization occurring during regeneration after 6-48 h. The normalization of perfusion independently of compression after 6 h may have implications for diagnostic and therapeutic strategies and for the better understanding of pathophysiological pathways in DOMS.

Twice-refocused stimulated echo diffusion imaging: Measuring diffusion time dependence at constant T1 weighting.

PURPOSE: Diffusion times longer than 50 ms are typically probed with stimulated-echo sequences. Varying the diffusion time in stimulated-echo sequences affects the T1 weighting of subcompartments, complicating the analysis of diffusion time dependence. Although inversion recovery preparation could be used to change the T1 weighting, it cannot ensure equal T1 weighting at arbitrary mixing times. In this article, a sequence that ensures constant T1 weighting over a wide range of diffusion times is presented. METHODS: The proposed sequence features 2 independent longitudinal storage periods: TM1 and TM2 . Diffusion encoding is performed during TM1 , effectively coupling the diffusion time and TM1 . Equal T1 weighting at arbitrary diffusion times is realized by keeping the total mixing time TM1 + TM2 constant. The sequence was compared with conventional stimulated-echo measurements of diffusion in a 2-compartment phantom consisting of distilled water and paraffinum perliquidum. Additionally, in vivo DTI of the brain was carried out for 8 healthy volunteers with diffusion times ranging from 50 to 500 ms. RESULTS: Diffusion time dependence of the axial and radial diffusivity was detected in the brain. Both sequences resulted in almost identical diffusivities in white matter. In regions containing partial volumes of gray and white matter, a dependency on T1 weighting was observed. CONCLUSION: In accordance with previous studies, little variance of T1 values appeared to be present in healthy white matter. However, this is likely different in diseased tissue. Here, the proposed sequence can be effective in differentiating between diffusion time dependence and T1 weighting effects.

On the Field Strength Dependence of Bi- and Triexponential Intravoxel Incoherent Motion (IVIM) Parameters in the Liver.

BACKGROUND: Studies on intravoxel incoherent motion (IVIM) imaging are carried out with different acquisition protocols. PURPOSE: To investigate the dependence of IVIM parameters on the B0 field strength when using a bi- or triexponential model. STUDY TYPE: Prospective. STUDY POPULATION: 20 healthy volunteers (age: 19-28 years). FIELD STRENGTH/SEQUENCE: Volunteers were examined at two field strengths (1.5 and 3T). Diffusion-weighted images of the abdomen were acquired at 24 b-values ranging from 0.2 to 500 s/mm2 . ASSESSMENT: ROIs were manually drawn in the liver. Data were fitted with a bi- and a triexponential IVIM model. The resulting parameters were compared between both field strengths. STATISTICAL TESTS: One-way analysis of variance (ANOVA) and Kruskal-Wallis test were used to test the obtained IVIM parameters for a significant field strength dependency. RESULTS: At b-values below 6 s/mm2 , the triexponential model provided better agreement with the data than the biexponential model. The average tissue diffusivity was D = 1.22/1.00 µm2 /msec at 1.5/3T. The average pseudodiffusion coefficients for the biexponential model were D* = 308/260 µm2 /msec at 1.5/3T; and for the triexponential model D1* = 81.3/65.9 µm2 /msec, D2* = 2453/2333 µm2 /msec at 1.5/3T. The average perfusion fractions for the biexponential model were f = 0.286/0.303 at 1.5/3T; and for the triexponential model f1 = 0.161/0.174 and f2 = 0.152/0.159 at 1.5/3T. A significant B0 dependence was only found for the biexponential pseudodiffusion coefficient (ANOVA/KW P = 0.037/0.0453) and tissue diffusivity (ANOVA/KW: P < 0.001). DATA CONCLUSION: Our experimental results suggest that triexponential pseudodiffusion coefficients and perfusion fractions obtained at different field strengths could be compared across different studies using different B0 . However, it is recommended to take the field strength into account when comparing tissue diffusivities or using the biexponential IVIM model. Considering published values for oxygenation-dependent transversal relaxation times of blood, it is unlikely that the two blood compartments of the triexponential model represent venous and arterial blood. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1883-1892.

Threshold Isocontouring on High b-Value Diffusion-Weighted Images in Magnetic Resonance Mammography.

OBJECTIVES: Motivated by the similar appearance of malignant breast lesions in high b-value diffusion-weighted imaging (DWI) and positron emission tomography, the purpose of this work was to evaluate the applicability of a threshold isocontouring approach commonly used in positron emission tomography to analyze DWI data acquired from female human breasts with minimal interobserver variability. METHODS: Twenty-three female participants (59.4 ± 10.0 years) with 23 lesions initially classified as suggestive of cancers in x-ray mammography screening were subsequently imaged on a 1.5-T magnetic resonance imaging scanner. Diffusion-weighted imaging was performed prior to biopsy with b values of 0, 100, 750, and 1500 s/mm. Isocontouring with different threshold levels was performed on the highest b-value image to determine the voxels used for subsequent evaluation of diffusion metrics. The coefficient of variation was computed by specifying 4 different regions of interest drawn around the lesion. Additionally, a receiver operating statistical analysis was performed. RESULTS: Using a relative threshold level greater than or equal to 0.85 almost completely suppresses the intra-individual and inter-individual variability. Among 4 studied diffusion metrics, the diffusion coefficients from the intravoxel incoherent motion model returned the highest area under curve value of 0.9. The optimal cut-off diffusivity was found to be 0.85 µm/ms with a sensitivity of 87.5% and specificity of 90.9%. CONCLUSION: Threshold isocontouring on high b-value maps is a viable approach to reliably evaluate DWI data of suspicious focal lesions in magnetic resonance mammography.

Radiomics Based on Adapted Diffusion Kurtosis Imaging Helps to Clarify Most Mammographic Findings Suspicious for Cancer.

Purpose To evaluate a radiomics model of Breast Imaging Reporting and Data System (BI-RADS) 4 and 5 breast lesions extracted from breast-tissue-optimized kurtosis magnetic resonance (MR) imaging for lesion characterization by using a sensitivity threshold similar to that of biopsy. Materials and Methods This institutional study included 222 women at two independent study sites (site 1: training set of 95 patients; mean age ± standard deviation, 58.6 years ± 6.6; 61 malignant and 34 benign lesions; site 2: independent test set of 127 patients; mean age, 58.2 years ± 6.8; 61 malignant and 66 benign lesions). All women presented with a finding suspicious for cancer at x-ray mammography (BI-RADS 4 or 5) and an indication for biopsy. Before biopsy, diffusion-weighted MR imaging (b values, 0-1500 sec/mm2) was performed by using 1.5-T imagers from different MR imaging vendors. Lesions were segmented and voxel-based kurtosis fitting adapted to account for fat signal contamination was performed. A radiomics feature model was developed by using a random forest regressor. The fixed model was tested on an independent test set. Conventional interpretations of MR imaging were also assessed for comparison. Results The radiomics feature model reduced false-positive results from 66 to 20 (specificity 70.0% [46 of 66]) at the predefined sensitivity of greater than 98.0% [60 of 61] in the independent test set, with BI-RADS 4a and 4b lesions benefiting from the analysis (specificity 74.0%, [37 of 50]; 60.0% [nine of 15]) and BI-RADS 5 lesions showing no added benefit. The model significantly improved specificity compared with the median apparent diffusion coefficient (P < .001) and apparent kurtosis coefficient (P = .02) alone. Conventional reading of dynamic contrast material-enhanced MR imaging provided sensitivity of 91.8% (56 of 61) and a specificity of 74.2% (49 of 66). Accounting for fat signal intensity during fitting significantly improved the area under the curve of the model (P = .001). Conclusion A radiomics model based on kurtosis diffusion-weighted imaging performed by using MR imaging machines from different vendors allowed for reliable differentiation between malignant and benign breast lesions in both a training and an independent test data set. © RSNA, 2018 Online supplemental material is available for this article.

Characterization of the diffusion coefficient of blood.

PURPOSE: To characterize the diffusion coefficient of human blood for accurate results in intravoxel incoherent motion imaging. METHODS: Diffusion-weighted MRI of blood samples from 10 healthy volunteers was acquired with a single-shot echo-planar-imaging sequence at body temperature. Effects of gradient profile (monopolar or flow-compensated), diffusion time (40-100 ms), and echo time (60-200 ms) were investigated. RESULTS: Although measured apparent diffusion coefficients of blood were larger for flow-compensated than for monopolar gradients, no dependence of the apparent diffusion coefficient on the diffusion time was found. Large differences between individual samples were observed, with results ranging from 1.26 to 1.66 µm2 /ms for flow-compensated and 0.94 to 1.52 µm2 /ms for monopolar gradients. Statistical analysis indicates correlations of the flow-compensated apparent diffusion coefficient with hematocrit (P = 0.007) and hemoglobin (P = 0.017), but not with mean corpuscular volume (P = 0.64). Results of Monte-Carlo simulations support the experimental observations. CONCLUSIONS: Measured blood apparent diffusion coefficient values depend on hematocrit/hemoglobin concentration and applied gradient profile due to non-Gaussian diffusion. Because in vivo measurement is delicate, an estimation based on blood count results could be an alternative. For intravoxel incoherent motion modeling, the use of a blood self-diffusion constant Db = 1.54 ± 0.12 µm2 /ms for flow-compensated and Db = 1.30 ± 0.18 µm2 /ms for monopolar encoding is suggested. Magn Reson Med 79:2752-2758, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Eddy current compensated double diffusion encoded (DDE) MRI.

PURPOSE: Eddy currents might lead to image distortions in diffusion-weighted echo planar imaging. A method is proposed to reduce their effects on double diffusion encoding (DDE) MRI experiments and the thereby derived microscopic fractional anisotropy (µFA). METHODS: The twice-refocused spin echo scheme was adapted for DDE measurements. To assess the effect of individual diffusion encodings on the image distortions, measurements of a grid of plastic rods in water were performed. The effect of eddy current compensation on µFA measurements was evaluated in the brains of six healthy volunteers. RESULTS: The use of an eddy current compensation reduced the signal variation. As expected, the distortions caused by the second encoding were larger than those of the first encoding, entailing a stronger need to compensate for them. For an optimal result, however, both encodings had to be compensated. The artifact reduction strongly improved the measurement of the µFA in ventricles and gray matter by reducing the overestimation. An effect of the compensation on absolute µFA values in white matter was not observed. CONCLUSION: It is advisable to compensate both encodings in DDE measurements for eddy currents. Magn Reson Med 77:328-335, 2017. © 2015 Wiley Periodicals, Inc.

Independent value of image fusion in unenhanced breast MRI using diffusion-weighted and morphological T2-weighted images for lesion characterization in patients with recently detected BI-RADS 4/5 x-ray mammography findings.

OBJECTIVES: The aim of this study was to evaluate the accuracy and applicability of solitarily reading fused image series of T2-weighted and high-b-value diffusion-weighted sequences for lesion characterization as compared to sequential or combined image analysis of these unenhanced sequences and to contrast- enhanced breast MRI. METHODS: This IRB-approved study included 50 female participants with suspicious breast lesions detected in screening X-ray mammograms, all of which provided written informed consent. Prior to biopsy, all women underwent MRI including diffusion-weighted imaging (DWIBS, b = 1500s/mm2). Images were analyzed as follows: prospective image fusion of DWIBS and T2-weighted images (FU), side-by-side analysis of DWIBS and T2-weighted series (CO), combination of the first two methods (CO+FU), and full contrast-enhanced diagnostic protocol (FDP). Diagnostic indices, confidence, and image quality of the protocols were compared by two blinded readers. RESULTS: Reading the CO+FU (accuracy 0.92; NPV 96.1 %; PPV 87.6 %) and the CO series (0.90; 96.1 %; 83.7 %) provided a diagnostic performance similar to the FDP (0.95; 96.1 %; 91.3 %; p > 0.05). FU reading alone significantly reduced the diagnostic accuracy (0.82; 93.3 %; 73.4 %; p = 0.023). CONCLUSIONS: MR evaluation of suspicious BI-RADS 4 and 5 lesions detected on mammography by using a non-contrast-enhanced T2-weighted and DWIBS sequence protocol is most accurate if MR images were read using the CO+FU protocol. KEY POINTS: • Unenhanced breast MRI with additional DWIBS/T2w-image fusion allows reliable lesion characterization. • Abbreviated reading of fused DWIBS/T2w-images alone decreases diagnostic confidence and accuracy. • Reading fused DWIBS/T2w-images as the sole diagnostic method should be avoided.

Flow-compensated intravoxel incoherent motion diffusion imaging.

PURPOSE: The pseudo-diffusion coefficient D* in intravoxel incoherent motion (IVIM) imaging was found difficult to seize. Flow-compensated diffusion gradients were used to test the validity of the commonly assumed biexponential limit and to determine not only D*, but also characteristic timescale τ and velocity v of the incoherent motion. THEORY AND METHODS: Bipolar and flow-compensated diffusion gradients were inserted into a flow-compensated single-shot EPI sequence. Images were obtained from a pipe-shaped flow phantom and from healthy volunteers. To calculate the IVIM signal outside the biexponential limit, a formalism based on normalized phase distributions was developed. RESULTS: The flow-compensated diffusion gradients caused less signal attenuation than the bipolar ones. A signal dependence on the duration of the flow-compensated gradients was found at low b-values in the volunteer datasets. The characteristic IVIM parameters were estimated to be v = 4.60 ± 0.34 mm/s and τ = 144 ± 10 ms for liver and v = 3.91 ± 0.54 mm/s and τ = 224 ± 47 ms for pancreas. CONCLUSION: Our results strongly indicate that the biexponential limit does not adequately model the diffusion signal in liver and pancreas. By using both bipolar and flow-compensated diffusion gradients of different duration, the characteristic timescale and velocity of the incoherent motion can be determined.

In vivo imaging of the time-dependent apparent diffusional kurtosis in the human calf muscle.

PURPOSE: To evaluate the time dependency of apparent diffusion coefficient Dapp and apparent diffusional kurtosis Kapp in vivo in the human calf. MATERIALS AND METHODS: Diffusion-weighted images of five healthy male volunteers were acquired using a 1.5T MR scanner. A stimulated echo sequence with echo planar imaging readout was used with diffusion gradients oriented along the three main axes. Mixing times (TM) of 100, 300, 500, and 700 ms and b-values ranging from 0 to 5600 s/mm(2) were used. Dapp and Kapp were determined. RESULTS: Dapp and Kapp decreased with increasing TM. As an example for absolute values, Dapp of the tibialis anterior drops from 1.18 ± 0.04 µm(2) /ms (TM = 100 ms) to 0.86 ± 0.02 µm(2) /ms (TM = 700 ms) (P = 0.001) and Kapp from 0.38 ± 0.06 to 0.32 ± 0.03 (P = 0.046) for a diffusion weighting along the left-right direction. Kapp was smaller than 0.43 in all muscles and at all TMs. CONCLUSION: The clearly observed time-dependence of Dapp and Kapp is an indicator of restricted diffusion in muscle tissue and may thus be a promising marker to investigate alterations of the microstructure. Compared to typical kurtosis values in white matter tissue of the brain, the kurtosis in muscle tissue is much smaller, which we attribute to the absence of the almost impermeable myelin sheath.

Influence of Magnetic Field Strength on Intravoxel Incoherent Motion Parameters in Diffusion MRI of the Calf.

Background: The purpose of this study was to investigate the dependence of Intravoxel Incoherent Motion (IVIM) parameters measured in the human calf on B0. Methods: Diffusion-weighted image data of eight healthy volunteers were acquired using five b-values (0-600 s/mm2) at rest and after muscle activation at 0.55 and 7 T. The musculus gastrocnemius mediale (GM, activated) was assessed. The perfusion fraction f and diffusion coefficient D were determined using segmented fits. The dependence on field strength was assessed using Student's t-test for paired samples and the Wilcoxon signed-rank test. A biophysical model built on the three non-exchanging compartments of muscle, venous blood, and arterial blood was used to interpret the data using literature relaxation times. Results: The measured perfusion fraction of the GM was significantly lower at 7 T, both for the baseline measurement and after muscle activation. For 0.55 and 7 T, the mean f values were 7.59% and 3.63% at rest, and 14.03% and 6.92% after activation, respectively. The biophysical model estimations for the mean proton-density-weighted perfusion fraction were 3.37% and 6.50% for the non-activated and activated states, respectively. Conclusions: B0 may have a significant effect on the measured IVIM parameters. The blood relaxation times suggest that 7 T IVIM may be arterial-weighted whereas 0.55 T IVIM may exhibit an approximately equal weighting of arterial and venous blood.

NMR-based diffusion pore imaging by double wave vector measurements.

One main interest of nuclear magnetic resonance (NMR) diffusion experiments is the investigation of boundaries such as cell membranes hindering the diffusion process. NMR diffusion measurements allow collecting the signal from the whole sample. This mainly eliminates the problem of vanishing signal at increasing resolution. It has been a longstanding question if, in principle, the exact shape of closed pores can be determined by NMR diffusion measurements. In this work, we present a method using short diffusion gradient pulses only, which is able to reveal the shape of arbitrary closed pores without relying on a priori knowledge. In comparison to former approaches, the method has reduced demands on relaxation times due to faster convergence to the diffusion long-time limit and allows for a more flexible NMR sequence design, because, e.g., stimulated echoes can be used.