Porcine circovirus type 2 infection promotes the SUMOylation of nucleophosmin-1 to facilitate the viral circular single-stranded DNA replication.

The mechanism of genome DNA replication in circular single-stranded DNA viruses is currently a mystery, except for the fact that it undergoes rolling-circle replication. Herein, we identified SUMOylated porcine nucleophosmin-1 (pNPM1), which is previously reported to be an interacting protein of the viral capsid protein, as a key regulator that promotes the genome DNA replication of porcine single-stranded DNA circovirus. Upon porcine circovirus type 2 (PCV2) infection, SUMO2/3 were recruited and conjugated with the K263 site of pNPM1's C-terminal domain to SUMOylate pNPM1, subsequently, the SUMOylated pNPM1 were translocated in nucleoli to promote the replication of PCV2 genome DNA. The mutation of the K263 site reduced the SUMOylation levels of pNPM1 and the nucleolar localization of pNPM1, resulting in a decrease in the level of PCV2 DNA replication. Meanwhile, the mutation of the K263 site prevented the interaction of pNPM1 with PCV2 DNA, but not the interaction of pNPM1 with PCV2 Cap. Mechanistically, PCV2 infection increased the expression levels of Ubc9, the only E2 enzyme involved in SUMOylation, through the Cap-mediated activation of ERK signaling. The upregulation of Ubc9 promoted the interaction between pNPM1 and TRIM24, a potential E3 ligase for SUMOylation, thereby facilitating the SUMOylation of pNPM1. The inhibition of ERK activation could significantly reduce the SUMOylation levels and the nucleolar localization of pNPM1, as well as the PCV2 DNA replication levels. These results provide new insights into the mechanism of circular single-stranded DNA virus replication and highlight NPM1 as a potential target for inhibiting PCV2 replication.

High-fidelity intravoxel incoherent motion parameter mapping using locally low-rank and subspace modeling.

PURPOSE: Intravoxel incoherent motion (IVIM) is a quantitative magnetic resonance imaging (MRI) method used to quantify perfusion properties of tissue non-invasively without contrast. However, clinical applications are limited by unreliable parameter estimates, particularly for the perfusion fraction (f) and pseudodiffusion coefficient (D*). This study aims to develop a high-fidelity reconstruction for reliable estimation of IVIM parameters. The proposed method is versatile and amenable to various acquisition schemes and fitting methods. METHODS: To address current challenges with IVIM, we adapted several advanced reconstruction techniques. We used a low-rank approximation of IVIM images and temporal subspace modeling to constrain the magnetization dynamics of the bi-exponential diffusion signal decay. In addition, motion-induced phase variations were corrected between diffusion directions and b-values, facilitating the use of high SNR real-valued diffusion data. The proposed method was evaluated in simulations and in vivo brain acquisitions in six healthy subjects and six individuals with a history of SARS-CoV-2 infection and compared with the conventionally reconstructed magnitude data. Following reconstruction, IVIM parameters were estimated voxel-wise. RESULTS: Our proposed method reduced noise contamination in simulations, resulting in a 60%, 58.9%, and 83.9% reduction in the NRMSE for D, f, and D*, respectively, compared to the conventional reconstruction. In vivo, anisotropic properties of D, f, and D* were preserved with the proposed method, highlighting microvascular differences in gray matter between individuals with a history of COVID-19 and those without (p = 0.0210), which wasn't observed with the conventional reconstruction. CONCLUSION: The proposed method yielded a more reliable estimation of IVIM parameters with less noise than the conventional reconstruction. Further, the proposed method preserved anisotropic properties of IVIM parameter estimates and demonstrated differences in microvascular perfusion in COVID-affected subjects, which weren't observed with conventional reconstruction methods.

High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting.

PURPOSE: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. METHODS: We developed 3D visualization of short transverse relaxation time component (ViSTa)-MRF, which combined ViSTa technique with MR fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multicompartment fitting that could introduce bias and/or noise from additional assumptions or priors. RESULTS: The in vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in vivo results of 1 mm- and 0.66 mm-isotropic resolution datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30× slower with lower SNR. Furthermore, we applied the proposed method to enable 5-min whole-brain 1 mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. CONCLUSIONS: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1 and 0.66 mm isotropic resolution in 5 and 15 min, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.

DTI-MR fingerprinting for rapid high-resolution whole-brain T1 , T2 , proton density, ADC, and fractional anisotropy mapping.

PURPOSE: This study aims to develop a high-efficiency and high-resolution 3D imaging approach for simultaneous mapping of multiple key tissue parameters for routine brain imaging, including T1 , T2 , proton density (PD), ADC, and fractional anisotropy (FA). The proposed method is intended for pushing routine clinical brain imaging from weighted imaging to quantitative imaging and can also be particularly useful for diffusion-relaxometry studies, which typically suffer from lengthy acquisition time. METHODS: To address challenges associated with diffusion weighting, such as shot-to-shot phase variation and low SNR, we integrated several innovative data acquisition and reconstruction techniques. Specifically, we used M1-compensated diffusion gradients, cardiac gating, and navigators to mitigate phase variations caused by cardiac motion. We also introduced a data-driven pre-pulse gradient to cancel out eddy currents induced by diffusion gradients. Additionally, to enhance image quality within a limited acquisition time, we proposed a data-sharing joint reconstruction approach coupled with a corresponding sequence design. RESULTS: The phantom and in vivo studies indicated that the T1 and T2 values measured by the proposed method are consistent with a conventional MR fingerprinting sequence and the diffusion results (including diffusivity, ADC, and FA) are consistent with the spin-echo EPI DWI sequence. CONCLUSION: The proposed method can achieve whole-brain T1 , T2 , diffusivity, ADC, and FA maps at 1-mm isotropic resolution within 10 min, providing a powerful tool for investigating the microstructural properties of brain tissue, with potential applications in clinical and research settings.

Optimized three-dimensional ultrashort echo time: Magnetic resonance fingerprinting for myelin tissue fraction mapping.

Quantitative assessment of brain myelination has gained attention for both research and diagnosis of neurological diseases. However, conventional pulse sequences cannot directly acquire the myelin-proton signals due to its extremely short T2 and T2* values. To obtain the myelin-proton signals, dedicated short T2 acquisition techniques, such as ultrashort echo time (UTE) imaging, have been introduced. However, it remains challenging to isolate the myelin-proton signals from tissues with longer T2. In this article, we extended our previous two-dimensional ultrashort echo time magnetic resonance fingerprinting (UTE-MRF) with dual-echo acquisition to three dimensional (3D). Given a relatively low proton density (PD) of myelin-proton, we utilized Cramér-Rao Lower Bound to encode myelin-proton with the maximal SNR efficiency for optimizing the MR fingerprinting design, in order to improve the sensitivity of the sequence to myelin-proton. In addition, with a second echo of approximately 3 ms, myelin-water component can be also captured. A myelin-tissue (myelin-proton and myelin-water) fraction mapping can be thus calculated. The optimized 3D UTE-MRF with dual-echo acquisition is tested in simulations, physical phantom and in vivo studies of both healthy subjects and multiple sclerosis patients. The results suggest that the rapidly decayed myelin-proton and myelin-water signal can be depicted with UTE signals of our method at clinically relevant resolution (1.8 mm isotropic) in 15 min. With its good sensitivity to myelin loss in multiple sclerosis patients demonstrated, our method for the whole brain myelin-tissue fraction mapping in clinical friendly scan time has the potential for routine clinical imaging.

Both noise-floor and tissue compartment difference in diffusivity contribute to FA dependence on b-value in diffusion MRI.

Noninvasive diffusion magnetic resonance imaging (dMRI) has been widely employed in both clinical and research settings to investigate brain tissue microstructure. Despite the evidence that dMRI-derived fractional anisotropy (FA) correlates with white matter properties, the metric is not specific. Recent studies have reported that FA is dependent on the b-value, and its origin has primarily been attributed to either the influence of microstructure or the noise-floor effect. A systematic investigation into the inter-relationship of these two effects is however still lacking. This study aims to quantify contributions of the reported differences in intra- and extra-neurite diffusivity to the observed changes in FA, in addition to the noise in measurements. We used in-vivo and post-mortem human brain imaging, as well as numerical simulations and histological validation, for this purpose. Our investigations reveal that the percentage difference of FA between b-values (pdFA) has significant positive associations with neurite density index (NDI), which is derived from in-vivo neurite orientation dispersion and density imaging (NODDI), or Bielschowsky's silver impregnation (BIEL) staining sections of fixed post-mortem human brain samples. Furthermore, such an association is found to be varied with Signal-to-Noise Ratio (SNR) level, indicating a nonlinear interaction effect between tissue microstructure and noise. Finally, a multicompartment model simulation revealed that these findings can be driven by differing diffusivities of intra- and extra-neurite compartments in tissue, with the noise-floor further amplifying the effect. In conclusion, both the differences in intra- and extra-neurite diffusivity and noise-floor effects significantly contribute to the FA difference associated with the b-value.

Rapid high-fidelity T 2 * mapping using single-shot overlapping-echo acquisition and deep learning reconstruction.

PURPOSE: To develop and evaluate a single-shot quantitative MRI technique called GRE-MOLED (gradient-echo multiple overlapping-echo detachment) for rapid T 2 * $$ {T}_2^{\ast } $$ mapping. METHODS: In GRE-MOLED, multiple echoes with different TEs are generated and captured in a single shot of the k-space through MOLED encoding and EPI readout. A deep neural network, trained by synthetic data, was employed for end-to-end parametric mapping from overlapping-echo signals. GRE-MOLED uses pure GRE acquisition with a single echo train to deliver T 2 * $$ {T}_2^{\ast } $$ maps less than 90 ms per slice. The self-registered B0 information modulated in image phase was utilized for distortion-corrected parametric mapping. The proposed method was evaluated in phantoms, healthy volunteers, and task-based FMRI experiments. RESULTS: The quantitative results of GRE-MOLED T 2 * $$ {T}_2^{\ast } $$ mapping demonstrated good agreement with those obtained from the multi-echo GRE method (Pearson's correlation coefficient = 0.991 and 0.973 for phantom and in vivo brains, respectively). High intrasubject repeatability (coefficient of variation <1.0%) were also achieved in scan-rescan test. Enabled by deep learning reconstruction, GRE-MOLED showed excellent robustness to geometric distortion, noise, and random subject motion. Compared to the conventional FMRI approach, GRE-MOLED also achieved a higher temporal SNR and BOLD sensitivity in task-based FMRI. CONCLUSION: GRE-MOLED is a new real-time technique for T 2 * $$ {T}_2^{\ast } $$ quantification with high efficiency and quality, and it has the potential to be a better quantitative BOLD detection method.

Free-breathing and instantaneous abdominal T2 mapping via single-shot multiple overlapping-echo acquisition and deep learning reconstruction.

OBJECTIVES: To develop a real-time abdominal T2 mapping method without requiring breath-holding or respiratory-gating. METHODS: The single-shot multiple overlapping-echo detachment (MOLED) pulse sequence was employed to achieve free-breathing T2 mapping of the abdomen. Deep learning was used to untangle the non-linear relationship between the MOLED signal and T2 mapping. A synthetic data generation flow based on Bloch simulation, modality synthesis, and randomization was proposed to overcome the inadequacy of real-world training set. RESULTS: The results from simulation and in vivo experiments demonstrated that our method could deliver high-quality T2 mapping. The average NMSE and R2 values of linear regression in the digital phantom experiments were 0.0178 and 0.9751. Pearson's correlation coefficient between our predicted T2 and reference T2 in the phantom experiments was 0.9996. In the measurements for the patients, real-time capture of the T2 value changes of various abdominal organs before and after contrast agent injection was realized. A total of 33 focal liver lesions were detected in the group, and the mean and standard deviation of T2 values were 141.1 ± 50.0 ms for benign and 63.3 ± 16.0 ms for malignant lesions. The coefficients of variance in a test-retest experiment were 2.9%, 1.2%, 0.9%, 3.1%, and 1.8% for the liver, kidney, gallbladder, spleen, and skeletal muscle, respectively. CONCLUSIONS: Free-breathing abdominal T2 mapping is achieved in about 100 ms on a clinical MRI scanner. The work paved the way for the development of real-time dynamic T2 mapping in the abdomen. KEY POINTS: • MOLED achieves free-breathing abdominal T2 mapping in about 100 ms, enabling real-time capture of T2 value changes due to CA injection in abdominal organs. • Synthetic data generation flow mitigates the issue of lack of sizable abdominal training datasets.

Single-shot multi-parametric mapping based on multiple overlapping-echo detachment (MOLED) imaging.

Multi-parametric quantitative magnetic resonance imaging (mqMRI) allows the characterization of multiple tissue properties non-invasively and has shown great potential to enhance the sensitivity of MRI measurements. However, real-time mqMRI during dynamic physiological processes or general motions remains challenging. To overcome this bottleneck, we propose a novel mqMRI technique based on multiple overlapping-echo detachment (MOLED) imaging, termed MQMOLED, to enable mqMRI in a single shot. In the data acquisition of MQMOLED, multiple MR echo signals with different multi-parametric weightings and phase modulations are generated and acquired in the same k-space. The k-space data is Fourier transformed and fed into a well-trained neural network for the reconstruction of multi-parametric maps. We demonstrated the accuracy and repeatability of MQMOLED in simultaneous mapping apparent proton density (APD) and any two parameters among T2, T2*, and apparent diffusion coefficient (ADC) in 130-170 ms. The abundant information delivered by the multiple overlapping-echo signals in MQMOLED makes the technique potentially robust to system imperfections, such as inhomogeneity of static magnetic field or radiofrequency field. Benefitting from the single-shot feature, MQMOLED exhibits a strong motion tolerance to the continuous movements of subjects. For the first time, it captured the synchronous changes of ADC, T2, and T1-weighted APD in contrast-enhanced perfusion imaging on patients with brain tumors, providing additional information about vascular density to the hemodynamic parametric maps. We expect that MQMOLED would promote the development of mqMRI technology and greatly benefit the applications of mqMRI, including therapeutics and analysis of metabolic/functional processes.

Optimized multi-axis spiral projection MR fingerprinting with subspace reconstruction for rapid whole-brain high-isotropic-resolution quantitative imaging.

PURPOSE: To improve image quality and accelerate the acquisition of 3D MR fingerprinting (MRF). METHODS: Building on the multi-axis spiral-projection MRF technique, a subspace reconstruction with locally low-rank constraint and a modified spiral-projection spatiotemporal encoding scheme called tiny golden-angle shuffling were implemented for rapid whole-brain high-resolution quantitative mapping. Reconstruction parameters such as the locally low-rank regularization parameter and the subspace rank were tuned using retrospective in vivo data and simulated examinations. B0 inhomogeneity correction using multifrequency interpolation was incorporated into the subspace reconstruction to further improve the image quality by mitigating blurring caused by off-resonance effect. RESULTS: The proposed MRF acquisition and reconstruction framework yields high-quality 1-mm isotropic whole-brain quantitative maps in 2 min at better quality compared with 6-min acquisitions of prior approaches. The proposed method was validated to not induce bias in T1 and T2 mapping. High-quality whole-brain MRF data were also obtained at 0.66-mm isotropic resolution in 4 min using the proposed technique, where the increased resolution was shown to improve visualization of subtle brain structures. CONCLUSIONS: The proposed tiny golden-angle shuffling, MRF with optimized spiral-projection trajectory and subspace reconstruction enables high-resolution quantitative mapping in ultrafast acquisition time.

Single-shell NODDI using dictionary-learner-estimated isotropic volume fraction.

Neurite orientation dispersion and density imaging (NODDI) enables the assessment of intracellular, extracellular, and free water signals from multi-shell diffusion MRI data. It is an insightful approach to characterize brain tissue microstructure. Single-shell reconstruction for NODDI parameters has been discouraged in previous studies caused by failure when fitting, especially for the neurite density index (NDI). Here, we investigated the possibility of creating robust NODDI parameter maps with single-shell data, using the isotropic volume fraction (fISO ) as a prior. Prior estimation was made independent of the NODDI model constraint using a dictionary learning approach. First, we used a stochastic sparse dictionary-based network (DictNet), which is trained with data obtained from in vivo and simulated diffusion MRI data, to predict fISO . In single-shell cases, the mean diffusivity and raw T2 signal with no diffusion weighting (S0 ) was incorporated in the dictionary for the fISO estimation. Then, the NODDI framework was used with the known fISO to estimate the NDI and orientation dispersion index (ODI). The fISO estimated using our model was compared with other fISO estimators in the simulation. Further, using both synthetic data simulation and human data collected on a 3 T scanner (both high-quality HCP and clinical dataset), we compared the performance of our dictionary-based learning prior NODDI (DLpN) with the original NODDI for both single-shell and multi-shell data. Our results suggest that DLpN-derived NDI and ODI parameters for single-shell protocols are comparable with original multi-shell NODDI, and the protocol with b = 2000 s/mm2 performs the best (error ~ 5% in white and gray matter). This may allow NODDI evaluation of studies on single-shell data by multi-shell scanning of two subjects for DictNet fISO training.

Whole-brain computational modeling reveals disruption of microscale brain dynamics in HIV infected individuals.

MRI-based neuroimaging techniques have been used to investigate brain injury associated with HIV-infection. Whole-brain cortical mean-field dynamic modeling provides a way to integrate structural and functional imaging outcomes, allowing investigation of microscale brain dynamics. In this study, we adopted the relaxed mean-field dynamic modeling to investigate structural and functional connectivity in 42 HIV-infected subjects before and after 12-week of combination antiretroviral therapy (cART) and compared them with 46 age-matched healthy subjects. Microscale brain dynamics were modeled by a set of parameters including two region-specific microscale brain properties, recurrent connection strengths, and subcortical inputs. We also analyzed the relationship between the model parameters (i.e., the recurrent connection and subcortical inputs) and functional network topological characterizations, including smallworldness, clustering coefficient, and network efficiency. The results show that untreated HIV-infected individuals have disrupted local brain dynamics that in part correlate with network topological measurements. Notably, after 12 weeks of cART, both the microscale brain dynamics and the network topological measurements improved and were closer to those in the healthy brain. This was also associated with improved cognitive performance, suggesting that improvement in local brain dynamics translates into clinical improvement.

Surface-Based Connectivity Integration: An atlas-free approach to jointly study functional and structural connectivity.

There has been increasing interest in jointly studying structural connectivity (SC) and functional connectivity (FC) derived from diffusion and functional MRI. Previous connectome integration studies almost exclusively required predefined atlases. However, there are many potential atlases to choose from and this choice heavily affects all subsequent analyses. To avoid such an arbitrary choice, we propose a novel atlas-free approach, named Surface-Based Connectivity Integration (SBCI), to more accurately study the relationships between SC and FC throughout the intra-cortical gray matter. SBCI represents both SC and FC in a continuous manner on the white surface, avoiding the need for prespecified atlases. The continuous SC is represented as a probability density function and is smoothed for better facilitation of its integration with FC. To infer the relationship between SC and FC, three novel sets of SC-FC coupling (SFC) measures are derived. Using data from the Human Connectome Project, we introduce the high-quality SFC measures produced by SBCI and demonstrate the use of these measures to study sex differences in a cohort of young adults. Compared with atlas-based methods, this atlas-free framework produces more reproducible SFC features and shows greater predictive power in distinguishing biological sex. This opens promising new directions for all connectomics studies.

Deep learning-based method for reducing residual motion effects in diffusion parameter estimation.

PURPOSE: Conventional motion-correction techniques for diffusion MRI can introduce motion-level-dependent bias in derived metrics. To address this challenge, a deep learning-based technique was developed to minimize such residual motion effects. METHODS: The data-rejection approach was adopted in which motion-corrupted data are discarded before model-fitting. A deep learning-based parameter estimation algorithm, using a hierarchical convolutional neural network (H-CNN), was combined with motion assessment and corrupted volume rejection. The method was designed to overcome the limitations of existing methods of this kind that produce parameter estimations whose quality depends strongly on a proportion of the data discarded. Evaluation experiments were conducted for the estimation of diffusion kurtosis and diffusion-tensor-derived measures at both the individual and group levels. The performance was compared with the robust approach of iteratively reweighted linear least squares (IRLLS) after motion correction with and without outlier replacement. RESULTS: Compared with IRLLS, the H-CNN-based technique is minimally sensitive to motion effects. It was tested at severe motion levels when 70% to 90% of the data are rejected and when random motion is present. The technique had a stable performance independent of the numbers and schemes of data rejection. A further test on a data set from children with attention-deficit hyperactivity disorder shows the technique can potentially ameliorate spurious group-level difference caused by head motion. CONCLUSION: This method shows great potential for reducing residual motion effects in motion-corrupted diffusion-weighted-imaging data, bringing benefits that include reduced bias in derived metrics in individual scans and reduced motion-level-dependent bias in population studies employing diffusion MRI.

Efficient T2 mapping with blip-up/down EPI and gSlider-SMS (T2 -BUDA-gSlider).

PURPOSE: To rapidly obtain high isotropic-resolution T2 maps with whole-brain coverage and high geometric fidelity. METHODS: A T2 blip-up/down EPI acquisition with generalized slice-dithered enhanced resolution (T2 -BUDA-gSlider) is proposed. A RF-encoded multi-slab spin-echo (SE) EPI acquisition with multiple TEs was developed to obtain high SNR efficiency with reduced TR. This was combined with an interleaved 2-shot EPI acquisition using blip-up/down phase encoding. An estimated field map was incorporated into the joint multi-shot EPI reconstruction with a structured low rank constraint to achieve distortion-free and robust reconstruction for each slab without navigation. A Bloch simulated subspace model was integrated into gSlider reconstruction and used for T2 quantification. RESULTS: In vivo results demonstrated that the T2 values estimated by the proposed method were consistent with gold standard spin-echo acquisition. Compared to the reference 3D fast spin echo (FSE) images, distortion caused by off-resonance and eddy current effects were effectively mitigated. CONCLUSION: BUDA-gSlider SE-EPI acquisition and gSlider-subspace joint reconstruction enabled distortion-free whole-brain T2 mapping in 2 min at ~1 mm3 isotropic resolution, which could bring significant benefits to related clinical and neuroscience applications.

Reproducibility of volume and asymmetry measurements of hippocampus, amygdala, and entorhinal cortex on traveling volunteers: a multisite MP2RAGE prospective study.

BACKGROUND: Multisite studies can considerably increase the pool of normally aging individuals with neurodegenerative disorders and thereby expedite the associated research. Understanding the reproducibility of the parameters of related brain structures-including the hippocampus, amygdala, and entorhinal cortex-in multisite studies is crucial in determining the impact of healthy aging or neurodegenerative diseases. PURPOSE: To estimate the reproducibility of the fascinating structures by automatic (FreeSurfer) and manual segmentation methods in a well-controlled multisite dataset. MATERIAL AND METHODS: Three traveling individuals were scanned at 10 sites, which were equipped with the same equipment (3T Prisma Siemens). They used the same scan protocol (two inversion-contrast magnetization-prepared rapid gradient echo sequences) and operators. Validity coefficients (intraclass correlations coefficient [ICC]) and spatial overlap measures (Dice Similarity Coefficient [DSC]) were used to estimate the reproducibility of multisite data. RESULTS: ICC and DSC values varied substantially among structures and segmentation methods, and values of manual tracing were relatively higher than the automated method. ICC and DSC values of structural parameters were greater than 0.80 and 0.60 across sites, as determined by manual tracing. Low reproducibility was observed in the amygdala parameters by automatic segmentation method (ICC = 0.349-0.529, DSC = 0.380-0.873). However, ICC and DSC scores of the hippocampus were higher than 0.60 and 0.65 by two segmentation methods. CONCLUSION: This study suggests that a well-controlled multisite study could provide a reliable MRI dataset. Manual tracing of volume assessments is recommended for low reproducibility structures that require high levels of precision in multisite studies.

MTE-NODDI: Multi-TE NODDI for disentangling non-T2-weighted signal fractions from compartment-specific T2 relaxation times.

Neurite orientation dispersion and density imaging (NODDI) has become a popular diffusion MRI technique for investigating microstructural alternations during brain development, maturation and aging in health and disease. However, the NODDI model of diffusion does not explicitly account for compartment-specific T2 relaxation and its model parameters are usually estimated from data acquired with a single echo time (TE). Thus, the NODDI-derived measures, such as the intra-neurite signal fraction, also known as the neurite density index, could be T2-weighted and TE-dependent. This may confound the interpretation of studies as one cannot disentangle differences in diffusion from those in T2 relaxation. To address this challenge, we propose a multi-TE NODDI (MTE-NODDI) technique, inspired by recent studies exploiting the synergy between diffusion and T2 relaxation. MTE-NODDI could give robust estimates of the non-T2-weighted signal fractions and compartment-specific T2 values, as demonstrated by both simulation and in vivo data experiments. Results showed that the estimated non-T2 weighted intra-neurite fraction and compartment-specific T2 values in white matter were consistent with previous studies. The T2-weighted intra-neurite fractions from the original NODDI were found to be overestimated compared to their non-T2-weighted estimates; the overestimation increases with TE, consistent with the reported intra-neurite T2 being larger than extra-neurite T2. Finally, the inclusion of the free water compartment reduces the estimation error in intra-neurite T2 in the presence of cerebrospinal fluid contamination. With the ability to disentangle non-T2-weighted signal fractions from compartment-specific T2 relaxation, MTE-NODDI could help improve the interpretability of future neuroimaging studies, especially those in brain development, maturation and aging.

Evaluation of the diffusion MRI white matter tract integrity model using myelin histology and Monte-Carlo simulations.

Quantitative evaluation of brain myelination has drawn considerable attention. Conventional diffusion-based magnetic resonance imaging models, including diffusion tensor imaging and diffusion kurtosis imaging (DKI),1 have been used to infer the microstructure and its changes in neurological diseases. White matter tract integrity (WMTI) was proposed as a biophysical model to relate the DKI-derived metrics to the underlying microstructure. Although the model has been validated on ex vivo animal brains, it was not well evaluated with ex vivo human brains. In this study, histological samples (namely corpus callosum) from postmortem human brains have been investigated based on WMTI analyses on a clinical 3T scanner and comparisons with gold standard myelin staining in proteolipid protein and Luxol fast blue. In addition, Monte Carlo simulations were conducted to link changes from ex vivo to in vivo conditions based on the microscale parameters of water diffusivity and permeability. The results show that WMTI metrics, including axonal water fraction AWF, radial extra-axonal diffusivity De⊥, and intra-axonal diffusivity Dawere needed to characterize myelin content alterations. Thus, WMTI model metrics are shown to be promising candidates as sensitive biomarkers of demyelination.

Phase-matched virtual coil reconstruction for highly accelerated diffusion echo-planar imaging.

PURPOSE: To propose a virtual coil (VC) acquisition/reconstruction framework to improve highly accelerated single-shot EPI (SS-EPI) and generalized slice dithered enhanced resolution (gSlider) acquisition in high-resolution diffusion imaging (DI). METHODS: For robust VC-GRAPPA reconstruction, a background phase correction scheme was developed to match the image phase of the reference data with the corrupted phase of the accelerated diffusion-weighted data, where the corrupted phase of the diffusion data varies from shot to shot. A Gy prewinding-blip was also added to the EPI acquisition, to create a shifted-ky sampling strategy that allows for better exploitation of VC concept in the reconstruction. To evaluate the performance of the proposed methods, 1.5 mm isotropic whole-brain SS-EPI and 860 µm isotropic whole-brain gSlider-EPI diffusion data were acquired at an acceleration of 8-9 fold. Conventional and VC-GRAPPA reconstructions were performed and compared, and corresponding g-factors were calculated. RESULTS: The proposed VC reconstruction substantially improves the image quality of both SS-EPI and gSlider-EPI, with reduced g-factor noise and reconstruction artifacts when compared to the conventional method. This has enabled high-quality low-noise diffusion imaging to be performed at 8-9 fold acceleration. CONCLUSIONS: The proposed VC acquisition/reconstruction framework improves the reconstruction of DI at high accelerations. The ability to now employ such high accelerations will allow DI with EPI at reduced distortion and faster scan time, which should be beneficial for many clinical and neuroscience applications.

Fast 3D brain MR fingerprinting based on multi-axis spiral projection trajectory.

PURPOSE: To develop a fast, sub-millimeter 3D magnetic resonance fingerprinting (MRF) technique for whole-brain quantitative scans. METHODS: An acquisition trajectory based on multi-axis spiral projection imaging (maSPI) was implemented for 3D MRF with steady-state precession and slab excitation. By appropriately assigning the in-plane and through-plane rotations of spiral interleaves in a novel acquisition scheme, an maSPI-based acquisition was implemented, and the total acquisition time was reduced by up to a factor of 8 compared to stack-of-spiral (SOS)-based acquisition. A sliding-window method was also used to further reduce the required number of time points for a faster acquisition. The experiments were conducted both on a phantom and in vivo. RESULTS: The results from the phantom measurements with the proposed and gold standard methods were consistent with a good linear correlation and an R2 value approaching 0.99. The in vivo experiments achieved whole-brain parametric maps with isotropic resolutions of 1 mm and 0.8 mm in 5.0 and 6.0 min, respectively, with potential for further acceleration. An in vivo experiment with intentionally moving subjects demonstrated that the maSPI scheme largely outperforms the SOS scheme in terms of robustness to head motion. CONCLUSION: 3D MRF with an maSPI acquisition scheme enables fast and robust scans for high-resolution parametric mapping.