White matter changes measured by multi-component MR Fingerprinting in multiple sclerosis.

T2-hyperintense lesions are the key imaging marker of multiple sclerosis (MS). Previous studies have shown that the white matter surrounding such lesions is often also affected by MS. Our aim was to develop a new method to visualize and quantify the extent of white matter tissue changes in MS based on relaxometry properties. We applied a fast, multi-parametric quantitative MRI approach and used a multi-component MR Fingerprinting (MC-MRF) analysis. We assessed the differences in the MRF component representing prolongedrelaxation time between patients with MS and controls and studied the relation between this component's volume and structural white matter damage identified on FLAIR MRI scans in patients with MS. A total of 48 MS patients at two different sites and 12 healthy controls were scanned with FLAIR and MRF-EPI MRI scans. MRF scans were analyzed with a joint-sparsity multi-component analysis to obtain magnetization fraction maps of different components, representing tissues such as myelin water, white matter, gray matter and cerebrospinal fluid. In the MS patients, an additional component was identified with increased transverse relaxation times compared to the white matter, likely representing changes in free water content. Patients with MS had a higher volume of the long- component in the white matter of the brain compared to healthy controls (B (95%-CI) = 0.004 (0.0006-0.008), p = 0.02). Furthermore, this MRF component had a moderate correlation (correlation coefficient R 0.47) with visible structural white matter changes on the FLAIR scans. Also, the component was found to be more extensive compared to structural white matter changes in 73% of MS patients. In conclusion, our MRF acquisition and analysis captured white matter tissue changes in MS patients compared to controls. In patients these tissue changes were more extensive compared to visually detectable white matter changes on FLAIR scans. Our method provides a novel way to quantify the extent of white matter changes in MS patients, which is underestimated using only conventional clinical MRI scans.

Mitigating undersampling errors in MR fingerprinting by sequence optimization.

PURPOSE: To develop a method for MR Fingerprinting (MRF) sequence optimization that takes both the applied undersampling pattern and a realistic reference map into account. METHODS: A predictive model for the undersampling error leveraging on perturbation theory was exploited to optimize the MRF flip angle sequence for improved robustness against undersampling artifacts. In this framework parameter maps from a previously acquired MRF scan were used as reference. Sequences were optimized for different sequence lengths, smoothness constraints and undersampling factors. Numerical simulations and in vivo measurements in eight healthy subjects were performed to assess the effect of the performed optimization. The optimized MRF sequences were compared to a conventionally shaped flip angle pattern and an optimized pattern based on the Cramér-Rao lower bound (CRB). RESULTS: Numerical simulations and in vivo results demonstrate that the undersampling errors can be suppressed by flip angle optimization. Analysis of the in vivo results show that a sequence optimized for improved robustness against undersampling with a flip angle train of length 400 yielded significantly lower median absolute errors in T 1 : 5 . 6 % ± 2 . 9 % and T 2 : 7 . 9 % ± 2 . 3 % compared to the conventional ( T 1 : 8 . 0 % ± 1 . 9 % , T 2 : 14 . 5 % ± 2 . 6 % ) and CRB-based ( T 1 : 21 . 6 % ± 4 . 1 % , T 2 : 31 . 4 % ± 4 . 4 % ) sequences. CONCLUSION: The proposed method is able to optimize the MRF flip angle pattern such that significant mitigation of the artifacts from strong k-space undersampling in MRF is achieved.

Multicomponent MR fingerprinting reconstruction using joint-sparsity and low-rank constraints.

PURPOSE: To develop an efficient algorithm for multicomponent MR fingerprinting (MC-MRF) reconstructions directly from highly undersampled data without making prior assumptions about tissue relaxation times and expected number of tissues. METHODS: The proposed method reconstructs MC-MRF maps from highly undersampled data by iteratively applying a joint-sparsity constraint to the estimated tissue components. Intermediate component maps are obtained by a low-rank multicomponent alternating direction method of multipliers (MC-ADMM) including the non-negativity of tissue weights as an extra regularization term. Over iterations, the used dictionary compression is adjusted. The proposed method (k-SPIJN) is compared with a two-step approach in which image reconstruction and multicomponent estimations are performed sequentially and tested in numerical simulations and in vivo by applying different undersampling factors in eight healthy volunteers. In the latter case, fully sampled data serves as the reference. RESULTS: The proposed method shows improved precision and accuracy in simulations compared with a state-of-art sequential approach. Obtained in vivo magnetization fraction maps for different tissue types show reduced systematic errors and reduced noise-like effects. Root mean square errors in estimated magnetization fraction maps significantly reduce from 13.0% ± $$ \pm $$ 5.8% with the conventional, two-step approach to 9.6% ± $$ \pm $$ 3.9% and 9.6% ± $$ \pm $$ 3.2% with the proposed MC-ADMM and k-SPIJN methods, respectively. Mean standard deviation in homogeneous white matter regions reduced significantly from 8.6% to 2.9% (two step vs. k-SPIJN). CONCLUSION: The proposed MC-ADMM and k-SPIJN reconstruction methods estimate MC-MRF maps from highly undersampled data resulting in improved image quality compared with the existing method.

Accelerated white matter lesion analysis based on simultaneous T1 and T2∗ quantification using magnetic resonance fingerprinting and deep learning.

PURPOSE: To develop an accelerated postprocessing pipeline for reproducible and efficient assessment of white matter lesions using quantitative magnetic resonance fingerprinting (MRF) and deep learning. METHODS: MRF using echo-planar imaging (EPI) scans with varying repetition and echo times were acquired for whole brain quantification of T1 and T2∗ in 50 subjects with multiple sclerosis (MS) and 10 healthy volunteers along 2 centers. MRF T1 and T2∗ parametric maps were distortion corrected and denoised. A CNN was trained to reconstruct the T1 and T2∗ parametric maps, and the WM and GM probability maps. RESULTS: Deep learning-based postprocessing reduced reconstruction and image processing times from hours to a few seconds while maintaining high accuracy, reliability, and precision. Mean absolute error performed the best for T1 (deviations 5.6%) and the logarithmic hyperbolic cosinus loss the best for T2∗ (deviations 6.0%). CONCLUSIONS: MRF is a fast and robust tool for quantitative T1 and T2∗ mapping. Its long reconstruction and several postprocessing steps can be facilitated and accelerated using deep learning.

Myelin water imaging from multi-echo T2 MR relaxometry data using a joint sparsity constraint.

Demyelination is the key pathological process in multiple sclerosis (MS). The extent of demyelination can be quantified with magnetic resonance imaging by assessing the myelin water fraction (MWF). However, long computation times and high noise sensitivity hinder the translation of MWF imaging to clinical practice. In this work, we introduce a more efficient and noise robust method to determine the MWF using a joint sparsity constraint and a pre-computed B1+-T2 dictionary. A single component analysis with this dictionary is used in an initial step to obtain a B1+ map. The T2 distribution is then determined from a reduced dictionary corresponding to the estimated B1+ map using a combination of a non-negativity and a joint sparsity constraint. The non-negativity constraint ensures that a feasible solution with non-negative contribution of each T2 component is obtained. The joint sparsity constraint restricts the T2 distribution to a small set of T2 relaxation times shared between all voxels and reduces the noise sensitivity. The applied Sparsity Promoting Iterative Joint NNLS (SPIJN) algorithm can be implemented efficiently, reducing the computation time by a factor of 50 compared to the commonly used regularized non-negative least squares algorithm. The proposed method was validated in simulations and in 8 healthy subjects with a 3D multi-echo gradient- and spin echo scan at 3 â€‹T. In simulations, the absolute error in the MWF decreased from 0.031 to 0.013 compared to the regularized NNLS algorithm for SNR â€‹= â€‹250. The in vivo results were consistent with values reported in literature and improved MWF-quantification was obtained especially in the frontal white matter. The maximum standard deviation in mean MWF in different regions of interest between subjects was smaller for the proposed method (0.0193) compared to the regularized NNLS algorithm (0.0266). In conclusion, the proposed method for MWF estimation is less computationally expensive and less susceptible to noise compared to state of the art methods. These improvements might be an important step towards clinical translation of MWF measurements.

Fast multi-component analysis using a joint sparsity constraint for MR fingerprinting.

PURPOSE: To develop an efficient algorithm for multi-component analysis of magnetic resonance fingerprinting (MRF) data without making a priori assumptions about the exact number of tissues or their relaxation properties. METHODS: Different tissues or components within a voxel are potentially separable in MRF because of their distinct signal evolutions. The observed signal evolution in each voxel can be described as a linear combination of the signals for each component with a non-negative weight. An assumption that only a small number of components are present in the measured field of view is usually imposed in the interpretation of multi-component data. In this work, a joint sparsity constraint is introduced to utilize this additional prior knowledge in the multi-component analysis of MRF data. A new algorithm combining joint sparsity and non-negativity constraints is proposed and compared to state-of-the-art multi-component MRF approaches in simulations and brain MRF scans of 11 healthy volunteers. RESULTS: Simulations and in vivo measurements show reduced noise in the estimated tissue fraction maps compared to previously proposed methods. Applying the proposed algorithm to the brain data resulted in 4 or 5 components, which could be attributed to different brain structures, consistent with previous multi-component MRF publications. CONCLUSIONS: The proposed algorithm is faster than previously proposed methods for multi-component MRF and the simulations suggest improved accuracy and precision of the estimated weights. The results are easier to interpret compared to voxel-wise methods, which combined with the improved speed is an important step toward clinical evaluation of multi-component MRF.

Gene expression and functional annotation of the human ciliary body epithelia.

PURPOSE: The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma. METHODS: We isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity. RESULTS: The gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (N)PE of 35 genes previously implicated in molecular mechanisms related to glaucoma. CONCLUSION: Our gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma.