Compensation of concomitant field effects in double diffusion encoding by means of added oscillating gradients.

Maxwell or concomitant fields imprint additional phases on the transverse magnetization. This concomitant phase may cause severe image artifacts like signal voids or distort the quantitative parameters due to the induced intravoxel dephasing. In particular, double diffusion encoding (DDE) schemes with two pairs of bipolar diffusion-weighting gradients separated by a refocusing radiofrequency (RF) pulse are prone to concomitant field-induced artifacts. In this work, a method for reducing concomitant field effects in these DDE sequences based on additional oscillating gradients is presented. These oscillating gradient pulses obtained by constrained optimization were added to the original gradient waveforms. The modified sequences reduced the accumulated concomitant phase without significant changes in the original sequence characteristics. The proposed method was applied to a DDE acquisition scheme consisting of 60 pairs of diffusion wave vectors. For phantom as well as for in vivo experiments, a considerable increase in the signal-to-noise ratio (SNR) was obtained. For phantom measurements with a diffusion weighting of b = 2000 s/mm2 for each of the gradient pairs, an SNR increase of up to 40% was observed for a transversal slice that had a distance of 5 cm from the isocenter. For equivalent slice parameters, in vivo measurements in the brain of a healthy volunteer exhibited an increase in SNR of up to 35% for b = 750 s/mm2 for each weighting. These findings are supported by corresponding simulations, which also predict a positive effect on the SNR. In summary, the presented method leads to an SNR gain without additional RF refocusing pulses.

Design of a high-performance non-linear gradient coil for diffusion weighted MRI of the breast.

Diffusion-weighted imaging (DWI) in the female breast is a magnetic resonance imaging (MRI) technique that complements clinical routine protocols, and that might provide an independent diagnostic value for specific clinical tasks in breast imaging. To further improve specificity of DWI in the breast, stronger and faster diffusion weighting is advantageous. Here, a dedicated gradient coil is designed, targeted at diffusion weighting in the female breast, with the peak gradient magnitude exceeding that of the current clinical MR scanners by an order of a magnitude. Design of application-tailored gradient coils in MRI has recently attracted increased attention. With the target application in mind, the gradient coil is designed on an irregularly shaped semi-open current-carrying surface. Due to the coil former closely fitting the non-spherical target region, non-linear encoding fields become particularly advantageous for achieving locally exceptionally high gradient strengths. As breast tissue has a predominantly isotropic cellular microstructure, the direction of the diffusion-weighting gradient may be allowed to vary within the target volume. However, due to the quadratic dependency of the b-factor on the gradient strength, variation of the gradient magnitude should be carefully controlled. To achieve the above design goals the corresponding multi-objective optimization problem is reformulated as a constrained optimization, allowing for flexible and precise control of the coil properties. A novel constraint is proposed, limiting gradient magnitude variation within every slice while allowing for variations in both the direction of the gradient within the slice and the magnitude across the slices. These innovations enable the design of a unilateral coil for diffusion weighting in the female breast with local gradient strengths exceeding 1 T/m with highly homogeneous diffusion weighting for imaging in the coronal slice orientation.

Diffusion Kurtosis Imaging-A Superior Approach to Assess Tumor-Stroma Ratio in Pancreatic Ductal Adenocarcinoma.

Extensive desmoplastic stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor progression and to the relative resistance of tumor cells towards (radio) chemotherapy. Thus, therapies that target the stroma are under intense investigation. To allow the stratification of patients who would profit from such therapies, non-invasive methods assessing the stroma content in relation to tumor mass are required. In the current prospective study, we investigated the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI), a radiologic method that measures the random motion of water molecules in tissue, in the assessment of PDAC lesions, and more specifically in the desmoplastic tumor stroma. We made use of a sophisticated DW-MRI approach, the so-called diffusion kurtosis imaging (DKI), which possesses potential advantages over conventional and widely used monoexponential diffusion-weighted imaging analysis (cDWI). We found that the diffusion constant D from DKI is highly negatively correlated with the percentage of tumor stroma, the latter determined by histology. D performed significantly better than the widely used apparent diffusion coefficient (ADC) from cDWI in distinguishing stroma-rich (>50% stroma percentage) from stroma-poor tumors (≤50% stroma percentage). Moreover, we could prove the potential of the diffusion constant D as a clinically useful imaging parameter for the differentiation of PDAC-lesions from non-neoplastic pancreatic parenchyma. Therefore, the diffusion constant D from DKI could represent a valuable non-invasive imaging biomarker for assessment of stroma content in PDAC, which is applicable for the clinical diagnostic of PDAC.

Temperature and concentration calibration of aqueous polyvinylpyrrolidone (PVP) solutions for isotropic diffusion MRI phantoms.

To use the "apparent diffusion coefficient" (Dapp) as a quantitative imaging parameter, well-suited test fluids are essential. In this study, the previously proposed aqueous solutions of polyvinylpyrrolidone (PVP) were examined and temperature calibrations were obtained. For example, at a temperature of 20°C, Dapp ranged from 1.594 (95% CI: 1.593, 1.595) µm2/ms to 0.3326 (95% CI: 0. 3304, 0.3348) µm2/ms for PVP-concentrations ranging from 10% (w/w) to 50% (w/w) using K30 polymer lengths. The temperature dependence of Dapp was found to be so strong that a negligence seems not advisable. The temperature dependence is descriptively modelled by an exponential function exp(c2 (T - 20°C)) and the determined c2 values are reported, which can be used for temperature calibration. For example, we find the value 0.02952 K-1 for 30% (w/w) PVP-concentration and K30 polymer length. In general, aqueous PVP solutions were found to be suitable to produce easily applicable and reliable Dapp-phantoms.

1D and 2D diffusion pore imaging on a preclinical MR system using adaptive rephasing: Feasibility and pulse sequence comparison.

Diffusion pore imaging (DPI) has recently been proposed as a means to acquire images of the average pore shape in an image voxel or region of interest. The highly asymmetric gradient scheme of its sequence makes it substantially demanding in terms of the hardware of the NMR system. The aim of this work is to show the feasibility of DPI on a preclinical 9.4T animal scanner. Using water-filled capillaries with an inner radius of 10µm, four different variants of the DPI sequence were compared in 1D and 2D measurements. The pulse sequences applied cover the basic implementation using one long and one temporally narrow gradient pulse, a CPMG-like variant with multiple refocusing RF pulses as well as two variants splitting up the long gradient and distributing it on either side of the refocusing pulse. Substantial differences between the methods were found in terms of signal-to-noise ratio, contrast, blurring, deviations from the expected results and sensitivity to gradient imperfections. Each of the tested sequences was found to produce characteristic gradient mismatches dependent on the absolute value, direction and sign of the applied q-value. Read gradients were applied to compensate these mismatches translating them into time shifts, which enabled 1D DPI yielding capillary radius estimations within the tolerances specified by the manufacturer. For a successful DPI application in 2D, a novel gradient amplitude adaption scheme was implemented to correct for the occurring time shifts. Using this adaption, higher conformity to the expected pore shape, reduced blurring and enhanced contrast were achieved. Images of the phantom's pore shape could be acquired with a nominal resolution of 2.2µm.

Evaluation of Diffusion Kurtosis Imaging Versus Standard Diffusion Imaging for Detection and Grading of Peripheral Zone Prostate Cancer.

OBJECTIVES: The purpose of the study was to evaluate and validate diffusion kurtosis imaging (DKI) for detection grading of peripheral zone prostate cancer (PCa) compared with standard diffusion-weighted imaging (DWI) in a cohort of patients with biopsy-proven PCa. MATERIALS AND METHODS: In this retrospective, single-institutional study, 55 patients (age, 67.5 ± 6.9 years; range, 52-84 years) who underwent multiparametric magnetic resonance imaging (MRI) before transperineal magnetic resonance/transrectal ultrasound-guided fusion biopsy were included. Suspicious lesions identified in multiparametric MRI underwent image-guided targeted biopsy procedure using a hybrid magnetic resonance/transrectal ultrasound-guided fusion biopsy system. Multiparametric MRI examinations were performed at 3.0 T using a 16-channel phased array coil. Diffusion kurtosis imaging has been acquired with 9 b values (0, 50, 250, 500, 750, 1000, 1250, 1500, and 2000 s/mm). In patients with histologically proven PCa, a representative tumor region was determined as region of interest (ROI) on axial T2-weighted images in consensus by 2 board-certified radiologists. For quantitative evaluation, ROIs located in malignant and contralateral tumor-free regions were transferred to diffusion-weighted images. Diffusion kurtosis imaging parameters (Dapp and Kapp) and apparent diffusion coefficient (ADC) values of the ROIs in tumor and contralateral remote areas were calculated. Estimation of the kurtosis-derived parameters was performed using a voxel-by-voxel fit followed by an ROI-based averaging and a second fit to ROI-averaged signal values. A subgroup analysis was performed to determine the influence of aggressiveness of PCa using ADC, Dapp, and Kapp. The receiver operating characteristic (ROC) curves were calculated for DKI parameters and ADC values. RESULTS: In the 55 patients, the average prostate-specific antigen level was 12.4 ± 12.6 ng/mL (range, 2.7­75.0 ng/mL), and the median Gleason score was 7 (range, 6­10). Dapp (units, 10(-3) mm(2)/s) was significantly lower in tumor compared with control regions (1.48 ± 0.35 vs 2.00 ± 0.32, P < 0.05), and Kapp was significantly higher (1.01 ± 0.21 vs 0.76 ± 0.14, P < 0.05). Dapp was significantly higher than standard ADC (units, 10(-3) mm(2)/s) both in tumor regions and in controls (1.48 ± 0.35 vs 1.10 ± 0.25 and 2.00 ± 0.32 vs 1.43 ± 0.25, P < 0.05). Neither the ROI-based calculation of the kurtosis parameters nor the application of the noise correction significantly changed the DKI parameter estimation. There was no significant difference for the applied fitting method for DKI-derived parameters considering the differentiation between tumor and control tissue. Subsequent ROC analyses did not reveal a significant difference between DKI and ADC for detection of PCa. Sensitivities derived by Youden J statistics cutoff values ranged from 69% to 91% for DKI parameters; specificities ranged from 71% to 89%. Subgroup analysis for DKI (Dapp, Kapp) and ADC for assessing aggressiveness of PCa found significant difference (P < 0.05) for discrimination between high- and low-grade findings. However, no significant difference could be obtained between standard DWI- and DKI-derived parameters. CONCLUSIONS: The results of this study demonstrated no significant benefit of DKI for detection and grading of PCa as compared with standard ADC in the peripheral zone determined from b values of 0 and 800 s/mm. For clinical routine application, ADC derived from monoexponential fitting of DWI data remains the standard for characterizing peripheral zone cancer of the prostate.

Diffusion pore imaging with generalized temporal gradient profiles.

In porous material research, one main interest of nuclear magnetic resonance diffusion (NMR) experiments is the determination of the shape of pores. While it has been a longstanding question if this is in principle achievable, it has been shown recently that it is indeed possible to perform NMR-based diffusion pore imaging. In this work we present a generalization of these previous results. We show that the specific temporal gradient profiles that were used so far are not unique as more general temporal diffusion gradient profiles may be used. These temporal gradient profiles may consist of any number of "short" gradient pulses, which fulfil the short-gradient approximation. Additionally, "long" gradient pulses of small amplitude may be present, which can be used to fulfil the rephasing condition for the complete profile. Some exceptions exist. For example, classical q-space gradients consisting of two short gradient pulses of opposite sign cannot be used as the phase information is lost due to the temporal antisymmetry of this profile.

Advanced fit of the diffusion kurtosis tensor by directional weighting and regularization.

The diffusional kurtosis is an indicator for diffusion restrictions in biological tissue. It is observed experimentally that the kurtosis is largest for directions perpendicular to the fiber direction in white matter. The directional dependence of the kurtosis can be described by the diffusion kurtosis tensor. Since the intention of diffusion kurtosis imaging is to detect diffusion restrictions, the fit of the kurtosis tensor should be dominated by directions perpendicular to the fibers. In this work, it is shown that the basic approach, which is solving the occurring linear system by a pseudoinverse matrix, may completely fail in this regard if the diffusion is highly anisotropic. This problem is solved by adapting the weights of the fit--and thus emphasizing directions of restricted water motion--using a direct fit of the kurtosis tensor to the measured kurtosis values. Moreover, due to its large number of degrees of freedom, the kurtosis tensor can assume complicated shapes resulting in a fit which is sensitive to noise. This article demonstrates that the quality of the kurtosis tensor calculation can be further improved if the fit is regularized by suppressing too large and too small kurtosis tensor values and thus restricting the possible tensor shapes.

Suppression of pulmonary vasculature in lung perfusion MRI using correlation analysis.

The purpose of the study was to evaluate the feasibility of suppressing the pulmonary vasculature in lung perfusion MRI using cross-correlation analysis (CCA). Perfusion magnetic resonance imaging (MRI) (3D FLASH, TR/TE/flip angle: 0.8 ms/2.1 ms/40 degrees ) of the lungs was performed in seven healthy volunteers at 1.5 Tesla after injection of Gd-DTPA. CCA was performed pixel-wise in lung segmentations using the signal time-course of the main pulmonary artery and left atrium as references. Pixels with high correlation coefficients were considered as arterial or venous and excluded from further analysis. Quantitative perfusion parameters [pulmonary blood flow (PBF) and volume (PBV)] were calculated for manual lung segmentations separately, with the entire left and right lung with all intrapulmonary vessels (IPV) included, excluded manually or excluded using CCA. The application of CCA allowed reliable suppression of hilar and large IPVs. Using vascular suppression by CCA, perfusion parameters were significantly reduced (p

New method for 3D parametric visualization of contrast-enhanced pulmonary perfusion MRI data.

Three-dimensional (3D) dynamic contrast-enhanced magnetic resonance imaging (3D DCE-MRI) has been proposed for the assessment of regional perfusion. The aim of this work was the implementation of an algorithm for a 3D parametric visualization of lung perfusion using different cutting planes and volume rendering. Our implementation was based on 3D DCE-MRI data of the lungs of five patients and five healthy volunteers. Using the indicator dilution theory, the regional perfusion parameters, tissue blood flow, blood volume and mean transit time were calculated. Due to the required temporal resolution, the volume elements of dynamic MR data sets show a reduced spatial resolution in the z-direction. Therefore, perfusion parameter volumes were interpolated. Linear interpolation and a combination of linear and nearest-neighbor interpolation were evaluated. Additionally, ray tracing was applied for 3D visualization. The linear interpolation algorithm caused interpolation errors at the lung borders. Using the combined interpolation, visualization of perfusion information in arbitrary cutting planes and in 3D using volume rendering was possible. This facilitated the localization of perfusion deficits compared with the coronal orientated source data. The 3D visualization of perfusion parameters using a combined interpolation algorithm is feasible. Further studies are required to evaluate the additional benefit from the 3D visualization.

Magnetic resonance imaging of uneven pulmonary perfusion in hypoxia in humans.

RATIONALE: Inhomogeneous hypoxic pulmonary vasoconstriction causing regional overperfusion and high capillary pressure is postulated for explaining how high pulmonary artery pressure leads to high-altitude pulmonary edema in susceptible (HAPE-S) individuals. OBJECTIVE: Because different species of animals also show inhomogeneous hypoxic pulmonary vasoconstriction, we hypothesized that inhomogeneity of lung perfusion in general increases in hypoxia, but is more pronounced in HAPE-S. For best temporal and spatial resolution, regional pulmonary perfusion was assessed by dynamic contrast-enhanced magnetic resonance imaging. METHODS: Dynamic contrast-enhanced magnetic resonance imaging and echocardiography were performed during normoxia and after 2 h of hypoxia (Fi(O2) = 0.12) in 11 HAPE-S individuals and 10 control subjects. As a measure for perfusion inhomogeneity, the coefficient of variation for two perfusion parameters (peak signal intensity, time-to-peak) was determined for the whole lung and isogravitational slices. RESULTS: There were no differences in perfusion inhomogeneity between the groups in normoxia. In hypoxia, analysis of coefficients of variation indicated a greater inhomogeneity in all subjects, which was more pronounced in HAPE-S compared with control subjects. Discrimination between HAPE-S and control subjects was best in gravity-dependent lung areas. Pulmonary artery pressure during hypoxia increased from 22 +/- 3 to 53 +/- 9 mm Hg in HAPE-S and 24 +/- 4 to 33 +/- 6 mm Hg in control subjects (mean +/- SD; p < 0.001), respectively. CONCLUSION: This study shows that hypoxic pulmonary vasoconstriction is inhomogeneous in hypoxia in humans, particularly in HAPE-S individuals where it is accompanied by a greater increase in pulmonary artery pressure compared with control subjects. These findings support the hypothesis of exaggerated and uneven hypoxic pulmonary vasoconstriction in HAPE-S individuals.

Intraindividual comparison of 1.0 M gadobutrol and 0.5 M gadopentetate dimeglumine for time-resolved contrast-enhanced three-dimensional magnetic resonance angiography of the upper torso.

PURPOSE: To compare the signal characteristics and bolus dynamics of 1.0 M gadobutrol and 0.5 M Gd-DTPA for time-resolved, three-dimensional, contrast-enhanced (CE) MRA of the upper torso. MATERIALS AND METHODS: Ten healthy volunteers were examined with time-resolved three-dimensional CE-MRA (scan time per three-dimensional data set: 0.86 second; voxel size: 3.6 x 2 x 6.3 mm(3)). Each volunteer underwent eight individual examinations after intravenous injection of 0.05 and 0.1 mmol/kg body weight (b.w.) of 1.0 M gadobutrol and 0.5 M Gd-DTPA using two injection rates (2.5 and 5 mL/second). The data analysis included quantitative measurements of the peak signal-to-noise ratio (SNR) and bolus dispersion (full width at half maximum (FWHM)) in the pulmonary artery, left atrium, and thoracic and abdominal aortas. RESULTS: No significant differences in the peak SNR and bolus dispersion were observed between gadobutrol and Gd-DTPA for all dose levels and injection rates in any of the vascular segments. For both contrast agents a dose of 0.1 mmol/kg b.w. injected with 5 mL/second achieved the highest SNR in all vascular segments. CONCLUSION: For the imaging parameters used in this study, higher-concentrated gadolinium chelates offer no relevant advantages for time-resolved three-dimensional CE-MRA of the upper torso.