David Kenkel

Systematic analysis of the intravoxel incoherent motion threshold separating perfusion and diffusion effects: Proposal of a standardized algorithm.

To systematically evaluate the dependence of intravoxel‐incoherent‐motion (IVIM) parameters on the b‐value threshold separating the perfusion and diffusion compartment, and to implement and test an algorithm for the standardized computation of this threshold.

Dynamic intravoxel incoherent motion imaging of skeletal muscle at rest and after exercise.

The purpose of this work was to demonstrate the feasibility of intravoxel incoherent motion imaging (IVIM) for non‐invasive quantification of perfusion and diffusion effects in skeletal muscle at rest and following exercise.

Functional Characterization of Germline Mutations in PDGFB and PDGFRB in Primary Familial Brain Calcification

Primary Familial Brain Calcification (PFBC), a neurodegenerative disease characterized by progressive pericapillary calcifications, has recently been linked to heterozygous mutations in PDGFB and PDGFRB genes. Here, we functionally analyzed several of these mutations in vitro. All six analyzed PDGFB mutations led to complete loss of PDGF-B function either through abolished protein synthesis or through defective binding and/or stimulation of PDGF-Rβ. The three analyzed PDGFRB mutations had more diverse consequences. Whereas PDGF-Rβ autophosphorylation was almost totally abolished in the PDGFRB L658P mutation, the two sporadic PDGFRB mutations R987W and E1071V caused reductions in protein levels and specific changes in the intensity and kinetics of PLCγ activation, respectively. Since at least some of the PDGFB mutations were predicted to act through haploinsufficiency, we explored the consequences of reduced Pdgfb or Pdgfrb transcript and protein levels in mice. Heterozygous Pdgfb or Pdgfrb knockouts, as well as double Pdgfb +/-;Pdgfrb +/- mice did not develop brain calcification, nor did Pdgfrb redeye/redeye mice, which show a 90% reduction of PDGFRβ protein levels. In contrast, Pdgfb ret/ret mice, which have altered tissue distribution of PDGF-B protein due to loss of a proteoglycan binding motif, developed brain calcifications. We also determined pericyte coverage in calcification-prone and non-calcification-prone brain regions in Pdgfb ret/ret mice. Surprisingly and contrary to our hypothesis, we found that the calcification-prone brain regions in Pdgfb ret/ret mice model had a higher pericyte coverage and a more intact blood-brain barrier (BBB) compared to non-calcification-prone brain regions. While our findings provide clear evidence that loss-of-function mutations in PDGFB or PDGFRB cause PFBC, they also demonstrate species differences in the threshold levels of PDGF-B/PDGF-Rβ signaling that protect against small-vessel calcification in the brain. They further implicate region-specific susceptibility factor(s) in PFBC pathogenesis that are distinct from pericyte and BBB deficiency.

Rapid and robust pulmonary proton ZTE imaging in the mouse

Pulmonary MRI is challenging because of the low proton density and rapid transverse relaxation in the lung associated with microscopic magnetic field inhomogeneities caused by tissue–air interfaces. Therefore, low signal is obtained in gradient and spin echo proton images. Alternatively, non‐proton MRI using hyperpolarized gases or radial techniques with ultrashort or zero TE have been proposed to image the lung. Also with the latter approach, the general challenge remains to provide full coverage of the lung at sufficient spatial resolution, signal‐to‐noise ratio (SNR) and image quality within a reasonable scan time. This task is further aggravated by physiological motion and is particularly demanding in small animals, such as mice. In this work, three‐dimensional (3D) zero echo time (ZTE) imaging is employed for efficient pulmonary MRI. Four protocols with different averaging and respiratory triggering schemes are developed and compared with respect to image quality and SNR. To address the critical issue of background signal in ZTE images, a subtraction approach is proposed, providing images virtually free of disturbing signal from nearby hardware parts. The protocols are tested for pulmonary MRI in six mice at 4.7 T, consistently providing images of high quality with a 3D isotropic resolution of 313 µm and SNR values in the lung between 8.0 and 18.5 within scan times between 1 min 21 s and 4 min 44 s. A generally high robustness of the ZTE approach against motion is observed, whilst respiratory triggering further improves the SNR and visibility of image details. The developed techniques are expected to enable efficient preclinical animal studies in the lung and will also be of importance for human applications. Further improvements are expected from radiofrequency (RF) coils with increased SNR and reduced background signal. Copyright

Whole-Body Diffusion Kurtosis Imaging: Initial Experience on Non-Gaussian Diffusion in Various Organs

IntroductionDiffusion kurtosis imaging (DKI) is based on a non-Gaussian diffusion model that should inherently better account for restricted water diffusion within the complex microstructure of most tissues than the conventional diffusion-weighted imaging (DWI), which presumes Gaussian distributed water molecule displacement probability. The aim of this investigation was to test the technical feasibility of in vivo whole-body DKI, probe for organ-specific differences, and compare whole-body DKI and DWI results. Materials and MethodsEight healthy subjects underwent whole-body DWI on a clinical 3.0 T magnetic resonance imaging system. Echo-planar images in the axial orientation were acquired at b-values of 0, 150, 300, 500, and 800 mm2/s. Parametrical whole-body maps of the diffusion coefficient (D), the kurtosis (K), and the traditional apparent diffusion coefficient (ADC) were generated. Goodness of fit was compared between DKI and DWI fits using the sums of squared residuals. Data groups were tested for significant differences of the mean by paired Student t tests. ResultsGood-quality parametrical whole-body maps of D, K, and ADC could be computed. Compared with ADC values, D values were significantly higher in the cerebral gray matter (by 30%) and white matter (27%), renal cortex (23%) and medulla (21%), spleen (101%), as well as erector spinae muscle (34%) (each P value <0.001). No significant differences between D and ADC were found in the cerebrospinal fluid (P = 0.08) and in the liver (P = 0.13). Curves of DKI fitted the measurement points significantly better than DWI curves did in most organs. ConclusionsWhole-body DKI is technically feasible and may reflect tissue microstructure more meaningfully than whole-body DWI.

Simultaneous Multislice Echo Planar Imaging With Blipped Controlled Aliasing in Parallel Imaging Results in Higher Acceleration A Promising Technique for Accelerated Diffusion Tensor Imaging of Skeletal Muscle

ObjectiveThe aim of this study was to investigate the feasibility of accelerated diffusion tensor imaging (DTI) of skeletal muscle using echo planar imaging (EPI) applying simultaneous multislice excitation with a blipped controlled aliasing in parallel imaging results in higher acceleration unaliasing technique. Materials and MethodsAfter federal ethics board approval, the lower leg muscles of 8 healthy volunteers (mean [SD] age, 29.4 [2.9] years) were examined in a clinical 3-T magnetic resonance scanner using a 15-channel knee coil. The EPI was performed at a b value of 500 s/mm2 without slice acceleration (conventional DTI) as well as with 2-fold and 3-fold acceleration. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in all 3 acquisitions. Fiber tracking performance was compared between the acquisitions regarding the number of tracks, average track length, and anatomical precision using multivariate analysis of variance and Mann-Whitney U tests. ResultsAcquisition time was 7:24 minutes for conventional DTI, 3:53 minutes for 2-fold acceleration, and 2:38 minutes for 3-fold acceleration. Overall FA and MD values ranged from 0.220 to 0.378 and 1.595 to 1.829 mm2/s, respectively. Two-fold acceleration yielded similar FA and MD values (P ≥ 0.901) and similar fiber tracking performance compared with conventional DTI. Three-fold acceleration resulted in comparable MD (P = 0.199) but higher FA values (P = 0.006) and significantly impaired fiber tracking in the soleus and tibialis anterior muscles (number of tracks, P < 0.001; anatomical precision, P ⩽ 0.005). ConclusionsSimultaneous multislice EPI with blipped controlled aliasing in parallel imaging results in higher acceleration can remarkably reduce acquisition time in DTI of skeletal muscle with similar image quality and quantification accuracy of diffusion parameters. This may increase the clinical applicability of muscle anisotropy measurements.

ZTE imaging with long-T2 suppression

Three‐dimensional radial zero echo time (ZTE) imaging enables efficient direct MRI of tissues with rapid transverse relaxation. Yet, the feature of capturing signals with a wide range of T2 and T2* values is accompanied by a lack of contrast between the corresponding tissues. In particular, the targeted short‐T2 tissues may not be easily identified, and various approaches have been proposed to generate T2 contrast by reducing the long‐T2 signal of water and/or fat. The aim of this work was to provide efficient long‐T2 suppression for selective direct MRI of short‐T2 tissues using the ZTE technique. For magnetization preparation, suppression pulses for water and fat were designed to provide both good T2 selectivity and off‐resonance performance. To obtain high efficiency at short TRs, the pulses were applied in a segmented sequence scheme with minimized timing overhead, thus leading to a quasi‐steady state of magnetization. The sequence timing was adjusted for optimal tissue contrast in musculoskeletal applications by means of simulations and experiments, incorporating both T2 and T1 of the involved tissues. The developed technique was employed for imaging of a lamb joint sample at 4.7 T. ZTE images were obtained with effective suppression of signals from tissues with long‐T2 water, such as muscle or articular spaces, and fat. Hence, primarily short‐T2 tissues were visible, such as bone and tendon. The MR image intensity of bone showed strong similarity with bone density imaged with micro‐computed tomography. Copyright

Hybrid PET/MR Imaging: An Algorithm to Reduce Metal Artifacts from Dental Implants in Dixon-Based Attenuation Map Generation Using a Multiacquisition Variable-Resonance Image Combination Sequence

It was the aim of this study to implement an algorithm modifying Dixon-based MR imaging datasets for attenuation correction in hybrid PET/MR imaging with a multiacquisition variable resonance image combination (MAVRIC) sequence to reduce metal artifacts. Methods: After ethics approval, in 8 oncologic patients with dental implants data were acquired in a trimodality setup with PET/CT and MR imaging. The protocol included a whole-body 3-dimensional dual gradient-echo sequence (Dixon) used for MR imaging–based PET attenuation correction and a high-resolution MAVRIC sequence, applied in the oral area compromised by dental implants. An algorithm was implemented correcting the Dixon-based μ maps using the MAVRIC in areas of Dixon signal voids. The artifact size of the corrected μ maps was compared with the uncorrected MR imaging μ maps. Results: The algorithm was robust in all patients. There was a significant reduction in mean artifact size of 70.5% between uncorrected and corrected μ maps from 697 ± 589 mm2 to 202 ± 119 mm2 (P = 0.016). Conclusion: The proposed algorithm could improve MR imaging–based attenuation correction in critical areas, when standard attenuation correction is hampered by metal artifacts, using a MAVRIC.

Characterization of trabecular bone density with ultra-short echo-time MRI at 1.5, 3.0 and 7.0 T--comparison with micro-computed tomography.

The goal of this study was to test the potential of ultra‐short echo‐time (UTE) MRI at 1.5, 3.0 and 7.0 T for depiction of trabecular bone structure (of the wrist bones), to evaluate whether T2* relaxation times of bone water and parametric maps of T2* of trabecular bone could be obtained at all three field strengths, and to compare the T2* relaxation times with structural parameters obtained from micro‐computed tomography (micro‐CT) as a reference standard. Ex vivo carpal bones of six wrists were excised en bloc and underwent MRI at 1.5, 3.0 and 7.0 T in a whole‐body MR imager using the head coil. A three‐dimensional radial fat‐suppressed UTE sequence was applied with subsequent acquisitions, with six different echo times TE of 150, 300, 600, 1200, 3500 and 7000 µs. The T2* relaxation time and pixel‐wise computed T2* parametric maps were compared with a micro‐computed‐tomography reference standard providing trabecular bone structural parameters including porosity (defined as the bone‐free fraction within a region of interest), trabecular thickness, trabecular separation, trabecular number and fractal dimension (Dk). T2* relaxation curves and parametric maps could be computed from datasets acquired at all field strengths. Mean T2* relaxation times of trabecular bone were 4580 ± 1040 µs at 1.5 T, 2420 ± 560 µs at 3.0 T and 1220 ± 300 µs at 7.0 T, when averaged over all carpal bones. A positive correlation of T2* with trabecular bone porosity and trabecular separation, and a negative correlation of T2* relaxation time with trabecular thickness, trabecular number and fractal dimension, was detected (p < 0.01 for all field strengths and micro‐CT parameters). We conclude that UTE MRI may be useful to characterize the structure of trabecular bone, comparable to micro‐CT. Copyright

Simultaneous multi-slice readout-segmented echo planar imaging for accelerated diffusion-weighted imaging of the breast.

OBJECTIVES Readout-segmented echo planar imaging (rs-EPI) significantly reduces susceptibility artifacts in diffusion-weighted imaging (DWI) of the breast compared to single-shot EPI but is limited by longer scan times. To compensate for this, we tested a new simultaneous multi-slice (SMS) acquisition for accelerated rs-EPI. MATERIALS AND METHODS After approval by the local ethics committee, eight healthy female volunteers (age, 38.9 ± 13.1 years) underwent breast MRI at 3T. Conventional as well as two-fold (2× SMS) and three-fold (3× SMS) slice-accelerated rs-EPI sequences were acquired at b-values of 50 and 800 s/mm(2). Two independent readers analyzed the apparent diffusion coefficient (ADC) in fibroglandular breast parenchyma. The signal-to-noise ratio (SNR) was estimated based on the subtraction method. ADC and SNR were compared between sequences by using the Friedman test. RESULTS The acquisition time was 4:21 min for conventional rs-EPI, 2:35 min for 2× SMS rs-EPI and 1:44 min for 3× SMS rs-EPI. ADC values were similar in all sequences (mean values 1.62 × 10(-3)mm(2)/s, p=0.99). Mean SNR was 27.7-29.6, and no significant differences were found among the sequences (p=0.83). CONCLUSION SMS rs-EPI yields similar ADC values and SNR compared to conventional rs-EPI at markedly reduced scan time. Thus, SMS excitation increases the clinical applicability of rs-EPI for DWI of the breast.