Description: Purpose To demonstrate that hyperpolarized (HP) xenon diffusion kurtosis imaging (DKI) is able to detect smoke-induced pulmonary lesions in rat models. Methods Multi-b DKI with hyperpolarized xenon was used for the first time in five smoke-exposed rats and five healthy rats. Additionally, DKI with b values of up to 80 s/cm 2 were used in two healthy rats to probe the critical b value (a limit beyond which the DKI cannot describe the non-Gaussian diffusion). Results The mean apparent diffusion coefficient (D app ) and diffusion kurtosis (K app ) extracted by the DKI model revealed significant changes in the smoke-exposed rats compared with those in the control group ( P  = 0.027 and 0.039, respectively), exhibiting strong correlations with mean linear intercept (L m ) from the histology. Although the maximum b value was increased to 80 s/cm 2 , the DKI could still describe the non-Gaussian diffusion (R 2  〉 0.97). Conclusion DKI with hyperpolarized xenon exhibited sensitivity in the detection of pulmonary lesions induced by smoke, including moderate emphysema and small airway diseases. The critical b value was rarely exceeded in DKI of the lungs due to the limited gradient strength of the MRI scanner used in our study. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Description: Purpose Optogenetic fMRI (ofMRI) is a novel tool in neurophysiology and neuroimaging. The method is prone to light-induced artifacts, two of which were investigated in this study. Methods ofMRI was performed in rats using two excitatory opsins (ChR2 and C1V1 TT ) virally transduced in somatosensory cortex or thalamus. Heat-induced apparent BOLD activation at the site of the optical fiber and stimulation light–induced activation of the visual pathways were investigated, and control experiments for these two artifacts were established. Results Specific optogenetic BOLD activation was observed with both opsins, accompanied by BOLD in the visual pathways. Unspecific heat-induced BOLD was ruled out by a control experiment employing low-level constant illumination in addition to pulsed optogenetic stimulation. Activation of the visual pathways was confirmed to be physiological by direct visual stimulation of the eyes and was suppressed by additional low-level constant light to the eyes. Light inside the brain was identified as one source of the BOLD signal observed in the visual pathways. Conclusion ofMRI is a method of tremendous potential, but unspecific activations in fMRI not caused by the activation of opsins must be avoided or recognized as such. The control experiments presented here allow for validating the specificity of optogenetic stimulation. Magn Reson Med 77:126–136, 2017. © 2016 Wiley Periodicals, Inc.

Description: Purpose To eliminate a slice-position–dependent excitation error commonly observed in bipolar-gradient composite excitations such as spokes pulses in parallel transmission. Theory and Methods An undesired timing delay between subpulses in the composite pulse and their bipolar slice-selective gradient is hypothesized to cause the error. A mathematical model is presented here to relate this mismatch to an induced slice-position–dependent phase difference between the subpulses. A new navigator method is proposed to measure the timing mismatch and eliminate the error. This is demonstrated at 7 Tesla with flip-angle maps measured by a presaturation turbo-flash sequence and in vivo images acquired by a simultaneous multislice/echo-planar imaging (SMS-EPI) sequence. Results Error-free flip-angle maps were obtained in two ways: 1) by correcting the time delay directly and 2) by applying the corresponding slice-position–dependent phase differences to the subpulses. This confirms the validity of the mathematical description. The radiofrequency (RF)-gradient delay measured by the navigator method was of 6.3 μs, which agreed well with the estimate from flip-angle maps at different delay times. By applying the timing correction, accurately excited EPI images were acquired with bipolar dual-spokes SMS-2 excitations. Conclusion An effective correction is proposed to mitigate slice-position–dependent errors in bipolar composite excitations caused by undesired RF-gradient timing delays. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Description: Purpose The robustness of a recently introduced globally convergent deconvolution algorithm with temporal and edge-preserving spatial regularization for the deconvolution of dynamic susceptibility contrast perfusion magnetic resonance imaging is assessed in the context of ischemic stroke. Theory and Methods Ischemic tissues are not randomly distributed in the brain but form a spatially organized entity. The addition of a spatial regularization term allows to take into account this spatial organization contrarily to the sole temporal regularization approach which processes each voxel independently. The robustness of the spatial regularization in relation to shape variability, hemodynamic variability in tissues, noise in the magnetic resonance imaging apparatus, and uncertainty on the arterial input function selected for the deconvolution is addressed via an original in silico validation approach. Results The deconvolution algorithm proved robust to the different sources of variability, outperforming temporal Tikhonov regularization in most realistic conditions considered. The limiting factor is the proper estimation of the arterial input function. Conclusion This study quantified the robustness of a spatio-temporal approach for dynamic susceptibility contrast-magnetic resonance imaging deconvolution via a new simulator. This simulator, now accessible online, is of wide applicability for the validation of any deconvolution algorithm. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Description: Purpose To investigate the feasibility of blood pressure difference measurement, ΔP, across the coronary artery using phase contrast (PC)-MRI for potential noninvasive assessment of the functional significance of coronary artery stenosis. Methods Three-directional velocities in the coronary arteries acquired using 2D-PC-MRI were used with the Navier-Stokes equations to derive ΔP. Repeat phantom studies were performed to assess the reproducibility of flow velocity and ΔP. ΔP derived using PC-MRI (ΔP MR ) and that obtained using pressure transducer (ΔP PT ) were compared. Reproducibility of coronary flow velocity was assessed in healthy controls (n = 11). Patients with suspected coronary artery disease (n = 6) were studied to evaluate the feasibility of ΔP MR measurement across a coronary stenosis. Results Phantom : Good overall reproducibility of flow velocity and ΔP measurements and excellent correlation (ΔP MR vs ΔP PT ) was observed: intraclass correlation (ICC) of 0.95(V z ), 0.72(V x ), 0.73(V y ), and 0.87(ΔP MR ) and R 2  = 0.94, respectively. Human : Good reproducibility of coronary flow velocity was observed: ICC of 0.94/0.95(V z ), 0.76/0.74(V x ), and 0.80/0.77(V y ) at cardiac phase 1/2. Significant ( p  = 0.025) increase in ΔP MR was observed in patients (6.40 ± 4.43 mmHg) versus controls (0.70 ± 0.57 mmHg). Conclusion ΔP MR in the coronary arteries is feasible. Upon further validation using the invasive measure, ΔP MR has the potential for noninvasive assessment of coronary artery stenosis. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Description: Purpose Assessment of brain hemodynamics without exogenous contrast agents is of increasing importance in clinical applications. This study aims to develop an MR perfusion technique that can provide noncontrast and multiparametric estimation of hemodynamic markers. Methods We devised an arterial spin labeling (ASL) method based on the principle of MR fingerprinting (MRF), referred to as MRF-ASL. By taking advantage of the rich information contained in MRF sequence, up to seven hemodynamic parameters can be estimated concomitantly. Feasibility demonstration, flip angle optimization, comparison with Look-Locker ASL, reproducibility test, sensitivity to hypercapnia challenge, and initial clinical application in an intracranial steno-occlusive process, Moyamoya disease, were performed to evaluate this technique. Results Magnetic resonance fingerprinting ASL provided estimation of up to seven parameters, including , tissue T 1 , cerebral blood flow (CBF), tissue bolus arrival time (BAT), pass-through arterial BAT, pass-through blood volume, and pass-through blood travel time. Coefficients of variation of the estimated parameters ranged from 0.2 to 9.6%. Hypercapnia resulted in an increase in CBF by 57.7%, and a decrease in BAT by 13.7 and 24.8% in tissue and vessels, respectively. Patients with Moyamoya disease showed diminished CBF and lengthened BAT that could not be detected with regular ASL. Conclusion Magnetic resonance fingerprinting ASL is a promising technique for noncontrast, multiparametric perfusion assessment. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Description: Purpose The purpose of this study is to accelerate an MR fingerprinting (MRF) acquisition by using a simultaneous multislice method. Methods A multiband radiofrequency (RF) pulse was designed to excite two slices with different flip angles and phases. The signals of two slices were driven to be as orthogonal as possible. The mixed and undersampled MRF signal was matched to two dictionaries to retrieve T 1 and T 2 maps of each slice. Quantitative results from the proposed method were validated with the gold-standard spin echo methods in a phantom. T 1 and T 2 maps of in vivo human brain from two simultaneously acquired slices were also compared to the results of fast imaging with steady-state precession based MRF method (MRF-FISP) with a single-band RF excitation. Results The phantom results showed that the simultaneous multislice imaging MRF–FISP method quantified the relaxation properties accurately compared to the gold-standard spin echo methods. T 1 and T 2 values of in vivo brain from the proposed method also matched the results from the normal MRF–FISP acquisition. Conclusion T 1 and T 2 values can be quantified at a multiband acceleration factor of two using our proposed acquisition even in a single-channel receive coil. Further acceleration could be achieved by combining this method with parallel imaging or iterative reconstruction. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Description: Purpose Magnetic resonance imaging (MRI)-based cell tracking has emerged as a useful tool for identifying the location of transplanted cells, and even their migration. Magnetically labeled cells appear as dark contrast in T2*-weighted MRI, with sensitivities of individual cells. One key hurdle to the widespread use of MRI-based cell tracking is the inability to determine the number of transplanted cells based on this contrast feature. In the case of single cell detection, manual enumeration of spots in three-dimensional (3D) MRI in principle is possible; however, it is a tedious and time-consuming task that is prone to subjectivity and inaccuracy on a large scale. This research presents the first comprehensive study on how a computer-based intelligent , automatic, and accurate cell quantification approach can be designed for spot detection in MRI scans. Methods Magnetically labeled mesenchymal stem cells (MSCs) were transplanted into rats using an intracardiac injection, accomplishing single cell seeding in the brain. T2*-weighted MRI of these rat brains were performed where labeled MSCs appeared as spots. Using machine learning and computer vision paradigms, approaches were designed to systematically explore the possibility of automatic detection of these spots in MRI. Experiments were validated against known in vitro scenarios. Results Using the proposed deep convolutional neural network (CNN) architecture, an in vivo accuracy up to 97.3% and in vitro accuracy of up to 99.8% was achieved for automated spot detection in MRI data. Conclusion The proposed approach for automatic quantification of MRI-based cell tracking will facilitate the use of MRI in large-scale cell therapy studies. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Description: Purpose To investigate the physical mechanisms associated with the contrast observed in neuromelanin MRI. Methods Phantoms having different concentrations of synthetic melanins with different degrees of iron loading were examined on a 3 Tesla scanner using relaxometry and quantitative magnetization transfer (MT). Results Concentration-dependent T 1 and T 2 shortening was most pronounced for the melanin pigment when combined with iron. Metal-free melanin had a negligible effect on the magnetization transfer spectra. On the contrary, the presence of iron-laden melanins resulted in a decreased magnetization transfer ratio. The presence of melanin or iron (or both) did not have a significant effect on the macromolecular content, represented by the pool size ratio. Conclusion The primary mechanism underlying contrast in neuromelanin-MRI appears to be the T 1 reduction associated with melanin-iron complexes. The macromolecular content is not significantly influenced by the presence of melanin with or without iron, and thus the MT is not directly affected. However, as T 1 plays a role in determining the MT-weighted signal, the magnetization transfer ratio is reduced in the presence of melanin-iron complexes. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.