T2 quantification in brain using 3D fast spin-echo imaging with long echo trains.

PURPOSE: Three-dimensional fast spin-echo (FSE) sequences commonly use very long echo trains (>64 echoes) and severely reduced refocusing angles. They are increasingly used in brain exams due to high, isotropic resolution and reasonable scan time when using long trains and short interecho spacing. In this study, T2 quantification in 3D FSE is investigated to achieve increased resolution when comparing with established 2D (proton-density dual-echo and multi-echo spin-echo) methods. METHODS: The FSE sequence design was explored to use long echo trains while minimizing T2 fitting error and maintaining typical proton density and T2 -weighted contrasts. Constant and variable flip angle trains were investigated using extended phase graph and Bloch equation simulations. Optimized parameters were analyzed in phantom experiments and validated in vivo in comparison to 2D methods for eight regions of interest in brain, including deep gray-matter structures and white-matter tracts. RESULTS: Phantom and healthy in vivo brain T2 measurements showed that optimized variable echo-train 3D FSE performs similarly to previous 2D methods, while achieving three-fold-higher slice resolution, evident visually in the 3D T2 maps. Optimization resulted in better T2 fitting and compared well with standard multi-echo spin echo (within the 8-ms confidence limits defined based on Bland-Altman analysis). CONCLUSION: T2 mapping using 3D FSE with long echo trains and variable refocusing angles provides T2 accuracy in agreement with 2D methods with additional high-resolution benefits, allowing isotropic views while avoiding incidental magnetization transfer effects. Consequently, optimized 3D sequences should be considered when choosing T2 mapping methods for high anatomic detail.

Bloch modelling enables robust T2 mapping using retrospective proton density and T2-weighted images from different vendors and sites.

T2 quantification is commonly attempted by applying an exponential fit to proton density (PD) and transverse relaxation (T2)-weighted fast spin echo (FSE) images. However, inter-site studies have noted systematic differences between vendors in T2 maps computed via standard exponential fitting due to imperfect slice refocusing, different refocusing angles and transmit field (B1+) inhomogeneity. We examine T2 mapping at 3T across 13 sites and two vendors in healthy volunteers from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using both a standard exponential and a Bloch modelling approach. The standard exponential approach resulted in highly variable T2 values across different sites and vendors. The two-echo fitting method based on Bloch equation modelling of the pulse sequence with prior knowledge of the nominal refocusing angles, slice profiles, and estimated B1+ maps yielded similar T2 values across sites and vendors by accounting for the effects of indirect and stimulated echoes. By modelling the actual refocusing angles used, T2 quantification from PD and T2-weighted images can be applied in studies across multiple sites and vendors.

T1 and T2 quantification from standard turbo spin echo images.

PURPOSE: To extract longitudinal and transverse (T1 and T2 ) relaxation maps from standard MRI methods. METHODS: Bloch simulations were used to model relative signal amplitudes from standard turbo spin-echo sequences: proton density weighted, T2 -weighted, and either T2 -weighted fluid attenuated inversion recovery or T1 -weighted images. Simulations over a range of expected parameter values yielded a look-up table of relative signal intensities of these sequences. Weighted images and flip angle maps were acquired in 8 subjects at 3 T using both single and multislice acquisitions. The T1 and T2 maps were fit by comparing the weighted images to the look-up table, given the measured flip angles. Results were compared with inversion recovery and multi-echo spin-echo experiments. RESULTS: A region analysis showed that relaxation maps computed from single-slice proton density, T2 and T1 weighting provided a mean T1 error of 4% in gray matter and 11% in white matter, and a mean T2 error of 3% and 4%, respectively, in comparison to reference measurements. In multislice acquisitions that are optimized to reduce cross-talk and incidental magnetization transfer, the mean T1 error was 7% in gray matter and 1% in white matter, and the mean T2 errors were 3% and 4%, respectively. The best T1 results were achieved using proton density, T2 and T1 weighting rather than the fluid attenuated inversion recovery, although T2 maps were largely unaffected by this choice. Incidental magnetization transfer reduced T1 accuracy in standard interleaved multislice acquisitions. CONCLUSION: Through exact sequence modeling and separate flip angle measurement, T2 and T1 may be quantified from a turbo spin-echo brain protocol with proton density, T2 , and T1 weighting.

Limitations of skipping echoes for exponential T2 fitting.

BACKGROUND: Exponential fitting of multiecho spin echo sequences with skipped echoes is still commonly used for quantification of transverse relaxation (T2 ). PURPOSE: To examine the efficacy of skipped echo methods for T2 quantification against computational modeling of the exact signal decay. STUDY TYPE: Prospective comparison of methods. SUBJECTS/PHANTOM: Eight volunteers were imaged at 4.7T, six volunteers at 1.5T, and phantoms ([MnCl2 ] = 68-270 mM). FIELD STRENGTH/SEQUENCE: 1.5T and 4.7T; multiple-echo spin echo. ASSESSMENT: Exponential fitting for T2 using all echoes, skipping the first echo or skipping all odd echoes, compared with Bloch simulations. Resulting T2 values were examined over a range of T2 (10-150 msec), refocusing flip angles (90-270°), and echo train lengths (ETL = 6-32). STATISTICAL TESTS: Shapiro-Wilk tests and Q-Q plots were used to check for normality of data. Paired sample t-tests and Wilcoxon rank tests were used to compare fitting models using α = 0.05. Multiple comparisons were accounted for with Bonferroni correction. RESULTS: In examined regions of interest, typical incorrect estimation of T2 ranged from 23-39% for exponential fitting of all echoes, or 15-32% for skipped echo methods. In vivo, T2 estimation error was reduced to as little as 10% with skipped echo methods using 180° refocusing and ETL = 8, although error varied due to refocusing angle, T2 , and ETL. In vivo, skipped echo T2 values were significantly different than all echo exponential fitting (P < 0.004), but also were significantly different from reference values (P < 0.002, except frontal white matter). Simulations showed skipping the first echo was the most effective form of exponential fitting, in particular for T2 <50 msec and ETL = 8, with potential to reduce T2 errors to 10%, depending on refocusing angle and T2 . DATA CONCLUSION: Skipping echoes is insufficient for avoiding stimulated echo contamination. Resulting T2 errors depend on a complicated interplay of T2 , refocusing angle, and ETL. Modeling of the multiecho sequence is recommended. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1432-1440.

Transverse relaxation and flip angle mapping: Evaluation of simultaneous and independent methods using multiple spin echoes.

PURPOSE: To evaluate transverse relaxation (T2) and flip angle maps derived from signal pathway modeling of multiple spin echoes using simultaneous or independent T2 and flip angle fitting. METHODS: We examined different approaches to indirect and stimulated echo compensated T2 relaxometry from multiple spin echoes to evaluate both T2 and flip angle accuracy in simulation, phantom, and human brain. Signal pathways were modeled with or without independent flip angle maps using either Bloch simulations, or Extended Phase Graph (EPG) with Fourier or Shinnar-Le Roux approximation of slice profiles. RESULTS: Slice-selective decay curves differ substantially between models. Inaccurate flip angles are obtained with EPG methods, although T2 values are relatively accurate. Providing measured flip angles to EPG methods yields erroneous T2. Bloch methods improve both T2 and flip angle results. Simultaneous fitting can suffer from flip angle redundancy yielding multiple T2 solutions, particularly in low signal-to-noise ratio cases. CONCLUSION: EPG fitting provides reasonably accurate T2, but is limited by poor accuracy in resulting flip angles, and T2 errors increase when flip angles are provided. Bloch simultaneous fitting of T2 and flip angle provides excellent results, but can be limited by multiple solutions which can be overcome by including a flip angle map. Magn Reson Med 77:2057-2065, 2017. © 2016 International Society for MagneticResonance in Medicine.

Recovery of accurate T2 from historical 1.5 tesla proton density and T2-weighted images: Application to 7-year T2 changes in multiple sclerosis brain.

OBJECTIVE: To determine accurate quantitative transverse relaxation times (T2) using retrospective clinical images and apply it to examine 7-year changes in multiple sclerosis (MS) brain. METHODS: A method for T2 mapping from retrospective proton density (PD) and T2-weighted fast spin echo images was recently introduced, but requires measurement of flip angles. We examined whether 1.5T flip angle variation in brain can be predicted, thus enabling T2 analysis of historical PD and T2-weighted images without a concurrent flip angle map. After method validation in healthy volunteers, retrospective longitudinal T2 analysis was performed in 14 MS subjects over seven years. Changes in patient T2 values were compared with brain atrophy, T2 lesion load and disability score in MS. RESULTS: Similar flip angle maps across volunteers enabled retrospective T2 from PD and T2-weighted images even when different refocusing angles were used. Over seven years, significant T2 changes of 2-4% were observed when using T2 modelling and the 7-year effect size for globus pallidus T2 was 0.56, which was more significant than brain atrophy. No significant T2 results were found when using exponential fit, which cannot account for refocusing angle variation. Moreover, change is T2 in globus pallidus and internal capsule correlated with MS disability score over time when using T2 modelling. CONCLUSIONS: Accurate quantitative T2 can be extracted from standard clinical 1.5T MRI exams that include PD and T2-weighted imaging even when no flip angle map is available. This method was applied retrospectively to examine seven year changes in MS.

Multi-modal magnetic resonance imaging and histology of vascular function in xenografts using macromolecular contrast agent hyperbranched polyglycerol (HPG-GdF).

Macromolecular gadolinium (Gd)-based contrast agents are in development as blood pool markers for MRI. HPG-GdF is a 583 kDa hyperbranched polyglycerol doubly tagged with Gd and Alexa 647 nm dye, making it both MR and histologically visible. In this study we examined the location of HPG-GdF in whole-tumor xenograft sections matched to in vivo DCE-MR images of both HPG-GdF and Gadovist. Despite its large size, we have shown that HPG-GdF extravasates from some tumor vessels and accumulates over time, but does not distribute beyond a few cell diameters from vessels. Fractional plasma volume (fPV) and apparent permeability-surface area product (aPS) parameters were derived from the MR concentration-time curves of HPG-GdF. Non-viable necrotic tumor tissue was excluded from the analysis by applying a novel bolus arrival time (BAT) algorithm to all voxels. aPS derived from HPG-GdF was the only MR parameter to identify a difference in vascular function between HCT116 and HT29 colorectal tumors. This study is the first to relate low and high molecular weight contrast agents with matched whole-tumor histological sections. These detailed comparisons identified tumor regions that appear distinct from each other using the HPG-GdF biomarkers related to perfusion and vessel leakiness, while Gadovist-imaged parameter measures in the same regions were unable to detect variation in vascular function. We have established HPG-GdF as a biocompatible multi-modal high molecular weight contrast agent with application for examining vascular function in both MR and histological modalities.

T2 quantification from only proton density and T2-weighted MRI by modelling actual refocusing angles.

Proton density and transverse relaxation (T2)-weighted fast spin echo images are frequently acquired. T2 quantification is commonly performed by applying an exponential fit to these two images, despite recent evidence that an exponential fit is insufficient to correctly quantify T2 in the presence of imperfect RF refocusing due to standard 2D slice selection or use of reduced refocusing angles. Here we examine the feasibility of accurate two echo fitting using standard proton density and T2-weighted images by utilizing Bloch equation simulations and prior knowledge of refocusing angles. This method is demonstrated in simulation, phantom, and human brain experiments, in comparison to the exponential approach, and to a 32 echo multiple-echo spin echo approach. Comparison to single spin echo is also performed in phantom experiments. The two echo method, which compensates for indirect and stimulated echoes, enables accurate quantitative T2 over a wide range of flip angle and T2 values using standard MRI methods, provided there is adequate SNR and flip angle knowledge.

Hyperbranched polyglycerols as trimodal imaging agents: design, biocompatibility, and tumor uptake.

Combining various imaging modalities often leads to complementary information and synergistic advantages. A trimodal long-circulating imaging agent tagged with radioactive, magnetic resonance, and fluorescence markers is able to combine the high sensitivity of SPECT with the high resolution of MRI over hours and days. The fluorescence marker helps to confirm the in vivo imaging information at the microscopic level, in the context of the tumor microenvironment. To make a trimodal long-circulating probe, high-molecular-weight hyperbranched polyglycerols (HPG) were modified with a suitable ligand for (111)In radiolabeling and Gd coordination, and additionally tagged with a fluorescent dye. The resulting radiopharmaceutical and contrast agent was nontoxic and hemocompatible. Measured radioactively, its total tumor uptake increased from 2.6% at 24 h to 7.3% at 72 h, which is twice the increase expected due to tumor growth in this time period. Both in vivo MRI and subsequent histological analyses of the same tumors confirmed maximum HPG accumulation at 3 days post injection. Furthermore, Gd-derivatized HPG has an excellent contrast enhancement on T1-weighted MRI at 10× lower molar concentrations than commercially available Galbumin. HPG derivatized with gadolinium, radioactivity, and fluorescence are thus long-circulating macromolecules with great potential for imaging of healthy and leaky blood vessels using overlapping multimodal approaches and for the passive targeting of tumors.

Bilateral filtering of magnetic resonance phase images.

High-pass filtering is required for the removal of background field inhomogeneities in magnetic resonance phase images. This high-pass filtering smooths across boundaries between areas with large differences in phase. The most prominent boundary is the surface of the brain where areas with large phase values inside the brain are located close to areas outside the brain where the phase is, on average, zero. Cortical areas, which are of great interest in brain MRI, are therefore often degraded by high-pass filtering. Here, we propose the use of the bilateral filter for the high-pass filtering step. The bilateral filter is essentially a Gaussian filter that stops smoothing at boundaries. We show that the bilateral filter improves image quality at the brain's surface, without sacrificing contrast within the brain.