Bulk and Mapping Speciation Analyses Unveil the Pattern and Heterogeneity of Cu Species during Organic Waste Treatment.

Organic wastes (OWs) can be a common source of copper (Cu) contamination of agricultural soils. Here we conducted a comprehensive study of 22 raw and treated OWs sampled at 6 different full-scale OW treatment plants. Bulk XANES analysis findings indicated that the Cu oxidation state was subject to changes throughout the OW treatment process, mostly depending on the anaerobic/aerobic conditions prevailing in each treatment stage. These changes were independent of the OW origin (agricultural, urban or industrial). Cu(I) prevailed in raw OWs and digestates (88-100%), whereas Cu(II) dominated in composts (46-100%). Bulk EXAFS analysis confirmed these observations and revealed that Cu(I) species in raw OWs and digestates consisted mainly of Cu(I)-sulfide (76-100%), while Cu(II) species (60-100%) in composts were Cu(II)-citrate, Cu(II)-carbonate and amorphous Cu(II)-phosphate. Interestingly, we observed that anaerobic digestion was conducive to the formation of crystallized Cu(I)-sulfides at the expense of nanosized and poorly crystalline Cu(I)-sulfide species, and that the recalcitrant Cu(I) species in composts was always crystallized Cu(I)-sulfide. XANES imaging analysis revealed Cu(II) species present in low proportions (2-4%) that were not detected using bulk XAS analysis in raw OWs and digestates. This demonstrated the potential of XANES imaging for probing minor species in complex matrices.

Patterned apoptosis has an instructive role for local growth and tissue shape regulation in a fast-growing epithelium.

What regulates organ size and shape remains one fundamental mystery of modern biology. Research in this area has primarily focused on deciphering the regulation in time and space of growth and cell division, while the contribution of cell death has been overall neglected. This includes studies of the Drosophila wing, one of the best-characterized systems for the study of growth and patterning, undergoing massive growth during larval stage and important morphogenetic remodeling during pupal stage. So far, it has been assumed that cell death was relatively neglectable in this tissue both during larval stage and pupal stage, and as a result, the pattern of growth was usually attributed to the distribution of cell division. Here, using systematic mapping and registration combined with quantitative assessment of clone size and disappearance as well as live imaging, we outline a persistent pattern of cell death and clone elimination emerging in the larval wing disc and persisting during pupal wing morphogenesis. Local variation of cell death is associated with local variation of clone size, pointing to an impact of cell death on local growth that is not fully compensated by proliferation. Using morphometric analyses of adult wing shape and genetic perturbations, we provide evidence that patterned death locally and globally affects adult wing shape and size. This study describes a roadmap for precise assessment of the contribution of cell death to tissue shape and outlines an important instructive role of cell death in modulating quantitatively local growth and morphogenesis of a fast-growing tissue.

Myelin bilayer mapping in the human brain in vivo.

PURPOSE: To quantitatively map the myelin lipid-protein bilayer in the live human brain. METHODS: This goal was pursued by integrating a multi-TE acquisition approach targeting ultrashort T2 signals with voxel-wise fitting to a three-component signal model. Imaging was performed at 3 T in two healthy volunteers using high-performance RF and gradient hardware and the HYFI sequence. The design of a suitable imaging protocol faced substantial constraints concerning SNR, imaging volume, scan time, and RF power deposition. Model fitting to data acquired using the proposed protocol was made feasible through simulation-based optimization, and filtering was used to condition noise presentation and overall depiction fidelity. RESULTS: A multi-TE protocol (11 TEs of 20-780 µs) for in vivo brain imaging was developed in adherence with applicable safety regulations and practical scan time limits. Data acquired using this protocol produced accurate model fitting results, validating the suitability of the protocol for this purpose. Structured, grainy texture of myelin bilayer maps was observed and determined to be a manifestation of correlated image noise resulting from the employed acquisition strategy. Map quality was significantly improved by filtering to uniformize the k-space noise distribution and simultaneously extending the k-space support. The final myelin bilayer maps provided selective depiction of myelin, reconciling competitive resolution (1.4 mm) with adequate SNR and benign noise texture. CONCLUSION: Using the proposed technique, quantitative maps of the myelin bilayer can be obtained in vivo. These maps offer unique information content with potential applications in basic research, diagnosis, disease monitoring, and drug development.

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.

Repeatability of Quantitative Knee Cartilage T1 , T2 , and T1ρ Mapping With 3D-MRI Fingerprinting.

BACKGROUND: Three-dimensional MR fingerprinting (3D-MRF) techniques have been recently described for simultaneous multiparametric mapping of knee cartilage. However, investigation of repeatability remains limited. PURPOSE: To assess the intra-day and inter-day repeatabilities of knee cartilage T1 , T2 , and T1ρ maps using a 3D-MRF sequence for simultaneous measurement. STUDY TYPE: Prospective. SUBJECTS: Fourteen healthy subjects (35.4 ± 9.3 years, eight males), scanned on Day 1 and Day 7. FIELD STRENGTH/SEQUENCE: 3 T/3D-MRF, T1 , T2 , and T1ρ maps. ASSESSMENT: The acquisition of 3D-MRF cartilage (simultaneous acquisition of T1 , T2 , and T1ρ maps) were acquired using a dictionary pattern-matching approach. Conventional cartilage T1 , T2 , and T1ρ maps were acquired using variable flip angles and a modified 3D-Turbo-Flash sequence with different echo and spin-lock times, respectively, and were fitted using mono-exponential models. Each sequence was acquired on Day 1 and Day 7 with two scans on each day. STATISTICAL TESTS: The mean and SD for cartilage T1 , T2 , and T1ρ were calculated in five manually segmented regions of interest (ROIs), including lateral femur, lateral tibia, medial femur, medial tibia, and patella cartilages. Intra-subject and inter-subject repeatabilities were assessed using coefficient of variation (CV) and intra-class correlation coefficient (ICC), respectively, on the same day and among different days. Regression and Bland-Altman analysis were performed to compare maps between the conventional and 3D-MRF sequences. RESULTS: The CV in all ROIs was lower than 7.4%, 8.4%, and 7.5% and the ICC was higher than 0.56, 0.51, and 0.52 for cartilage T1 , T2 , and T1ρ , respectively. The MRF results had a good agreement with the conventional methods with a linear regression slope >0.61 and R2 > 0.59. CONCLUSION: The 3D-MRF sequence had high intra-subject and inter-subject repeatabilities for simultaneously measuring knee cartilage T1 , T2 , and T1ρ with good agreement with conventional sequences. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Finding an effective MRI sequence to visualise the electroporated area in plant-based models by quantitative mapping.

Plant-based models can reduce the number of animal studies for electroporation research in medical cancer treatment modalities like irreversible electroporation. Magnetic resonance imaging (MRI) provides volumetric visualisation of electroporated animal or plant tissues; however, contrast behaviour is complex, depending on tissue and sequence parameters. This study numerically analysed contrast between electroporated and non-electroporated tissue at 1.5 T in various MRI sequences (DWI, T1W, T2W, T2*W, PDW, FLAIR) performed 4 h after electroporation in apples (N = 4) and potatoes (N = 8). Sequence parameters (inversion time [TI], echo time [TE], b-value) for optimal contrast and electroporation-mediated changes in T1 and T2 relaxation times and apparent diffusion coefficient (ADC) were determined for potato (N = 4) using quantitative parameter mapping. FLAIR showed the electroporated zone in potatoes with best contrast, whereas no sequence yielded clear visibility in apples. After electroporation, T1 and T2 in potato decreased by 29% ([1245 ± 54 to 886 ± 119] ms) and 12% ([249 ± 17 to 217 ± 12] ms), respectively. ADC increased by 11% ([1303 ± 25 to 1449 ± 28] × 10-6 mm2/s). Optimal contrast was found for TI = 1000 ms, low TE and high b-value. T1 was most sensitive to EP-mediated tissue changes. Future research could use this methodology and findings to obtain high-contrast MR images of electroporated and non-electroporated biological tissues.

msQSM: Morphology-based self-supervised deep learning for quantitative susceptibility mapping.

Quantitative susceptibility mapping (QSM) has been applied to the measurement of iron deposition and the auxiliary diagnosis of neurodegenerative disease. There still exists a dipole inversion problem in QSM reconstruction. Recently, deep learning approaches have been proposed to resolve this problem. However, most of these approaches are supervised methods that need pairs of the input phase and ground-truth. It remains a challenge to train a model for all resolutions without using the ground-truth and only using one resolution data. To address this, we proposed a self-supervised QSM deep learning method based on morphology. It consists of a morphological QSM builder to decouple the dependency of the QSM on acquisition resolution, and a morphological loss to reduce artifacts effectively and save training time efficiently. The proposed method can reconstruct arbitrary resolution QSM on both human data and animal data, regardless of whether the resolution is higher or lower than that of the training set. Our method outperforms the previous best unsupervised method with a 3.6% higher peak signal-to-noise ratio, 16.2% lower normalized root mean square error, and 22.1% lower high-frequency error norm. The morphological loss reduces training time by 22.1% with respect to the cycle gradient loss used in the previous unsupervised methods. Experimental results show that the proposed method accurately measures QSM with arbitrary resolutions, and achieves state-of-the-art results among unsupervised deep learning methods. Research on applications in neurodegenerative diseases found that our method is robust enough to measure significant increase in striatal magnetic susceptibility in patients during Alzheimer's disease progression, as well as significant increase in substantia nigra susceptibility in Parkinson's disease patients, and can be used as an auxiliary differential diagnosis tool for Alzheimer's disease and Parkinson's disease.

Updates on Compositional MRI Mapping of the Cartilage: Emerging Techniques and Applications.

Osteoarthritis (OA) is a widely occurring degenerative joint disease that is severely debilitating and causes significant socioeconomic burdens to society. Magnetic resonance imaging (MRI) is the preferred imaging modality for the morphological evaluation of cartilage due to its excellent soft tissue contrast and high spatial resolution. However, its utilization typically involves subjective qualitative assessment of cartilage. Compositional MRI, which refers to the quantitative characterization of cartilage using a variety of MRI methods, can provide important information regarding underlying compositional and ultrastructural changes that occur during early OA. Cartilage compositional MRI could serve as early imaging biomarkers for the objective evaluation of cartilage and help drive diagnostics, disease characterization, and response to novel therapies. This review will summarize current and ongoing state-of-the-art cartilage compositional MRI techniques and highlight emerging methods for cartilage compositional MRI including MR fingerprinting, compressed sensing, multiexponential relaxometry, improved and robust radio-frequency pulse sequences, and deep learning-based acquisition, reconstruction, and segmentation. The review will also briefly discuss the current challenges and future directions for adopting these emerging cartilage compositional MRI techniques for use in clinical practice and translational OA research studies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

A preliminary diagnostic accuracy study of quantitative MRI biomarkers for differentiating parotid tumor types.

Background: Differentiating among the different types of parotid tumors on imaging is useful for guiding clinical disposition, which ultimately may lead to surgical management. The goal of this study was to determine whether quantitative T2 signal characteristics and morphologic features on magnetic resonance imaging (MRI) can serve as predictive biomarkers for distinguishing between tumor types. Methods: A retrospective review of T2-weighted MRIs in patients with pathology-proven parotid tumors was performed. Quantitative T2 maps and surface regularity measurements of the tumors were obtained via semi-automated regions of interest (ROI). Linear Discriminant Analysis was used to populate the receiver operating characteristics (ROCs) curves for these variables. A P value of <0.05 was considered to be significant. Results: A total of 35 tumors (21 benign and 14 malignant neoplasms) were included in this analysis. For differentiating the benign versus malignant classes of parotid tumors, T2 signal and surface regularity combined yielded an area under the curve of 0.62 (P value: 0.2) through the ROC analysis. However, for the pleomorphic adenomas versus other types of parotid tumors, using both T2 signal and surface regularity yielded an area under the curve of 0.81 (P value: 0.007) through the ROC analysis. Conclusions: T2 signal and surface regularity combined can significantly differentiate pleomorphic adenomas from other types of parotid tumors and can potentially be used as a predictive imaging biomarker.

Three-dimensional multi-parameter brain mapping using MR fingerprinting.

The purpose of this study was to develop and test a 3D multi-parameter MR fingerprinting (MRF) method for brain imaging applications. The subject cohort included 5 healthy volunteers, repeatability tests done on 2 healthy volunteers and tested on two multiple sclerosis (MS) patients. A 3D-MRF imaging technique capable of quantifying T1, T2 and T1ρ was used. The imaging sequence was tested in standardized phantoms and 3D-MRF brain imaging with multiple shots (1, 2 and 4) in healthy human volunteers and MS patients. Quantitative parametric maps for T1, T2, T1ρ, were generated. Mean gray matter (GM) and white matter (WM) ROIs were compared for each mapping technique, Bland-Altman plots and intra-class correlation coefficient (ICC) were used to assess repeatability and Student T-tests were used to compare results in MS patients. Standardized phantom studies demonstrated excellent agreement with reference T1/T2/T1ρ mapping techniques. This study demonstrates that the 3D-MRF technique is able to simultaneously quantify T1, T2 and T1ρ for tissue property characterization in a clinically feasible scan time. This multi-parametric approach offers increased potential to detect and differentiate brain lesions and to better test imaging biomarker hypotheses for several neurological diseases, including MS.

Cardiac magnetic resonance imaging before and after therapeutic interventions for systemic sclerosis-associated myocarditis.

OBJECTIVES: Cardiac magnetic resonance imaging (CMRI) is increasingly used to evaluate cardiac involvement in SSc. We assessed changes, including inflammatory and/or fibrotic myocardial lesions detected by CMRI, following therapeutic interventions for SSc-associated symptomatic myocarditis. METHODS: In this retrospective study, myocarditis was diagnosed by CMRI (2018 revised Lake Louise criteria) in 14 diffuse and 4 limited SSc patients [16/18 women, age 56 years (s.d. 11), disease duration 8 years (s.d. 11), 17/18 with lung involvement] with cardiac symptoms and abnormal findings on echocardiography (4/18) and/or in 24-hour Holter monitoring (12/14). CMRI was repeated after 8 months (s.d. 3) following administration of cyclophosphamide (n = 11, combined with corticosteroids in 3 and rituximab in 1), mycophenolate (n = 1), tocilizumab (n = 1), methotrexate/corticosteroids (n = 2), corticosteroids (n = 1) or autologous stem cell transplantation (n = 2). RESULTS: Functional cardiac improvement was evident by increases in left [by 5.8% (s.d. 7.8), P = 0.006] and right ventricular ejection fraction [by 4.5% (s.d. 11.4), P = 0.085] in the second CMRI compared with the first. Notably, late gadolinium enhancement, currently considered to denote replacement fibrosis, decreased by 3.1% (s.d. 3.8; P = 0.003), resolving in six patients. Markers of myocardial oedema, namely T2 ratio and T2 mapping, decreased by 0.27 (s.d. 0.40; P = 0.013) and 6.0 (s.d. 7; P = 0.025), respectively. Conversely, both T1 mapping, considered to reflect acute oedema and diffuse fibrosis, and extracellular volume fraction, reflecting diffuse fibrosis, remained unchanged. CONCLUSIONS: CMRI may distinguish between reversible inflammatory/fibrotic and irreversible fibrotic lesions in SSc patients with active myocarditis, confirming the unique nature of primary cardiac involvement in SSc. Whether, and how, CMRI should be used to monitor treatment effects in SSc-associated myocarditis warrants further study.

Self Supervised Denoising Diffusion Probabilistic Models for Abdominal DW-MRI.

Quantitative diffusion weighted MRI in the abdomen provides important markers of disease, however significant limitations exist for its accurate computation. One such limitation is the low signal-to-noise ratio, particularly at high diffusion b-values. To address this, multiple diffusion directional images can be collected at each b-value and geometrically averaged, which invariably leads to longer scan time, blurring due to motion and other artifacts. We propose a novel parameter estimation technique based on self supervised diffusion denoising probabilistic model that can effectively denoise diffusion weighted images and work on single diffusion gradient direction images. Our source code is made available at https://github.com/quin-med-harvard-edu/ssDDPM.

Synthetic MRI in the detection and quantitative evaluation of sacroiliac joint lesions in axial spondyloarthritis.

Objective: Our primary objective was to verify the hypothesis that synthetic magnetic resonance imaging (MRI) is similar to conventional MRI in detecting sacroiliac joint lesions in patients with axial spondyloarthritis (axSpA). A secondary objective was to assess the quantitative value of synthetic mapping in bone marrow edema (BME) and fat metaplasia. Methods: A total of 132 axSpA patients who underwent synthetic and conventional MRI from October 2019 to March 2021 were included in this prospective study. Two independent readers visually evaluated active inflammatory (BME, capsulitis, enthesitis, and inflammation at site of erosion) and structural lesions (erosion, sclerosis, ankylosis, and fat metaplasia) of the sacroiliac joints on conventional and synthetic magnetic resonance (MR) images. In addition, T1, T2, and proton density (PD) values, which were generated by synthetic mapping, were used to further quantitatively evaluate BME and fat metaplasia. A McNemar test was used to compare the differences between the two methods in the detection of sacroiliac joint lesions. Intraclass correlation coefficients (ICCs) were used to assess the inter-reader consistency of quantitative values. Mann-Whitney tests were performed, and receiver operating characteristic (ROC) curves were created for all quantitative analyses. Results: There were no statistical difference between synthetic and conventional MRI in the detection of sacroiliac joint lesions (all p-values > 0.05). A total of 103 images of BME and 111 images of fat metaplasia were quantitatively evaluated using T1, T2, and PD values. The consistency of quantitative values among readers was good (ICC 0.903-0.970). T1 and T2 values were consistently higher in BME than in normal marrow (p < 0.001), but PD values were not significantly different (p = 0.830). T2 and PD values were higher in fat metaplasia than in normal marrow, but T1 values were lower (p < 0.001). In the case of BME, T1 values had greater diagnostic efficiency [area under the curve (AUC) 0.99] than T2 values (AUC 0.78). There were no significant differences in the diagnostic efficiency of T1 (AUC 0.88), T2 (AUC 0.88), and PD (AUC 0.88) values in the case of fat metaplasia. Conclusion: Synthetic MRI is as effective as conventional MRI in detecting sacroiliac joint lesions in patients with axSpA. Furthermore, synthetic mapping can accurately quantify BME and fat metaplasia.

Development of a novel 10-echo multi-contrast sequence based on EPIK to deliver simultaneous quantification of T2 and T2* with application to oxygen extraction fraction.

PURPOSE: The simultaneous quantification of T2 and T2 * maps based on fast sequences for combined GE and SE acquisition has rekindled research and clinical interest by offering a wide range of attractive applications, e.g., dynamic tracking of oxygen extraction fraction (OEF). However, previously published methods based on EPI-readouts have been hindered by resolution and the number of acquired echoes. METHODS: This work presents a novel 10-echo GE-SE EPIK (EPI with keyhole) sequence for the rapid quantification of T2 '. T2 /T2 * maps from the GE-SE EPIK sequence were validated using three phantoms and 15 volunteers at 3T. The incorporation of a sliding window approach, combined with the full sampling of the k-space center inherent to EPIK, enables a high effective temporal resolution. That is, for an eight-slice breath-hold experiment, a temporal sampling rate of eight reconstructed slices per 1.1 s. RESULTS: In comparison with repeated single-echo SE, multi-echo GE, and spectroscopy methods, the GE-SE EPIK sequence shows good agreement in quantifying T2 /T2 * values, while the gray matter/white matter separation yielded the expected contrast differentiation. The OEF was calculated with a view to an initial application with clinical relevance, producing results comparable to those in the literature and with good sensitivity in breath-hold experiments. CONCLUSIONS: GE-SE EPIK provides increased resolution and more echoes, including two SEs, than comparable sequences. Moreover, GE-SE EPIK achieves this within an acquisition time of 57 s for 20 slices (matrix size = 128×128; FOV = 24 cm) and with a reasonably short TE for the final echo (114 ms). The sequence can dynamically track OEF changes in a breath-hold experiment.

Multicenter Repeatability and Reproducibility of MR Fingerprinting in Phantoms and in Prostatic Tissue.

PURPOSE: To evaluate multicenter repeatability and reproducibility of T1 and T2 maps generated using MR fingerprinting (MRF) in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI system phantom and in prostatic tissues. METHODS: MRF experiments were performed on 5 different 3 Tesla MRI scanners at 3 different institutions: University Hospitals Cleveland Medical Center (Cleveland, OH), Brigham and Women's Hospital (Boston, MA) in the United States, and Diagnosticos da America (Rio de Janeiro, RJ) in Brazil. Raw MRF data were reconstructed using a Gadgetron-based MRF online reconstruction pipeline to yield quantitative T1 and T2 maps. The repeatability of T1 and T2 values over 6 measurements in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI system phantom was assessed to demonstrate intrascanner variation. The reproducibility between the 4 clinical scanners was assessed to demonstrate interscanner variation. The same-day test-retest normal prostate mean T1 and T2 values from peripheral zone and transitional zone were also compared using the intraclass correlation coefficient and Bland-Altman analysis. RESULTS: The intrascanner variation of values measured using MRF was less than 2% for T1 and 4.7% for T2 for relaxation values, within the range of 307.7 to 2360 ms for T1 and 19.1 to 248.5 ms for T2 . Interscanner measurements showed that the T1 variation was less than 4.9%, and T2 variation was less than 8.1% between multicenter scanners. Both T1 and T2 values in in vivo prostatic tissue demonstrated high test-retest reliability (intraclass correlation coefficient > 0.92) and strong linear correlation (R2  > 0.840). CONCLUSION: Prostate MRF measurements of T1 and T2 are repeatable and reproducible between MRI scanners at different centers on different continents for the above measurement ranges.

Correcting for imaging gradients-related bias of T2 relaxation times at high-resolution MRI.

PURPOSE: High-resolution animal imaging is an integral part of preclinical drug development and the investigation of diseases' pathophysiology. Quantitative mapping of T2 relaxation times (qT2 ) is a valuable tool for both preclinical and research applications, providing high sensitivity to subtle tissue pathologies. High-resolution T2 mapping, however, suffers from severe underestimation of T2 values due to molecular diffusion. This affects both single-echo and multi-echo spin echo (SSE and MESE), on top of the well-known contamination of MESE signals by stimulated echoes, and especially on high-field and preclinical scanners in which high imaging gradients are used in comparison to clinical scanners. METHODS: Diffusion bias due to imaging gradients was analyzed by quantifying the effective b-value for each coherence pathway in SSE and MESE protocols, and incorporating this information in a joint T2 -diffusion reconstruction algorithm. Validation was done on phantoms and in vivo mouse brain using a 9.4T and a 7T MRI scanner. RESULTS: Underestimation of T2 values due to strong imaging gradients can reach up to 70%, depending on scan parameters and on the sample's diffusion coefficient. The algorithm presented here produced T2 values that agreed with reference spectroscopic measurements, were reproducible across scan settings, and reduced the average bias of T2 values from -33.5 ± 20.5% to -0.1 ± 3.6%. CONCLUSIONS: A new joint T2 -diffusion reconstruction algorithm is able to negate imaging gradient-related underestimation of T2 values, leading to reliable mapping of T2 values at high resolutions.

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.

A Cyclodextrin-Hosted Ir(III) Complex for Ratiometric Mapping of Tumor Hypoxia In Vivo.

Hypoxia is considered as a key microenvironmental feature of solid tumors. Luminescent transition metal complexes particularly those based on iridium and ruthenium have shown remarkable potentials for constructing sensitive oxygen-sensing probes due to their unique oxygen quenching pathway. However, the low aqueous solubility of these complexes largely retards their sensing applications in biological media. Moreover, it remains difficult so far to use the existing complexes typically possessing only one luminescent domain to quantitatively detect the intratumoral hypoxia degree. Herein, an Ir(III) complex showing red emissions is designed and synthesized, and innovatively encapsulated within a hydrophobic pocket of Cyanine7-modified cyclodextrin. The Ir(III) complex enables the oxygen detection, while the cyclodextrin is used not only for improving the water solubility and suppressing the luminescence quenching effect of the surrounding aqueous media, but also for carrying Cyanine7 to establish a ratiometric oxygen fluorescence probe. 2D nuclear magnetic resonance is carried out to confirm the host-guest structure. The oxygen-responsive ability of the resulting ratiometric probe is evaluated through in vitro cell and multicellular experiments. Further animal studies about tumor oxygen level mapping demonstrate that the probe can be successfully used for quantitatively visualizing tumor hypoxia in vivo.

Non-linear fitting with joint spatial regularization in arterial spin labeling.

Multi-Delay single-shot arterial spin labeling (ASL) imaging provides accurate cerebral blood flow (CBF) and, in addition, arterial transit time (ATT) maps but the inherent low SNR can be challenging. Especially standard fitting using non-linear least squares often fails in regions with poor SNR, resulting in noisy estimates of the quantitative maps. State-of-the-art fitting techniques improve the SNR by incorporating prior knowledge in the estimation process which typically leads to spatial blurring. To this end, we propose a new estimation method with a joint spatial total generalized variation regularization on CBF and ATT. This joint regularization approach utilizes shared spatial features across maps to enhance sharpness and simultaneously improves noise suppression in the final estimates. The proposed method is evaluated at three levels, first on synthetic phantom data including pathologies, followed by in vivo acquisitions of healthy volunteers, and finally on patient data following an ischemic stroke. The quantitative estimates are compared to two reference methods, non-linear least squares fitting and a state-of-the-art ASL quantification algorithm based on Bayesian inference. The proposed joint regularization approach outperforms the reference implementations, substantially increasing the SNR in CBF and ATT while maintaining sharpness and quantitative accuracy in the estimates.

A multi-inversion multi-echo spin and gradient echo echo planar imaging sequence with low image distortion for rapid quantitative parameter mapping and synthetic image contrasts.

PURPOSE: Brain imaging exams typically take 10-20 min and involve multiple sequential acquisitions. A low-distortion whole-brain echo planar imaging (EPI)-based approach was developed to efficiently encode multiple contrasts in one acquisition, allowing for calculation of quantitative parameter maps and synthetic contrast-weighted images. METHODS: Inversion prepared spin- and gradient-echo EPI was developed with slice-order shuffling across measurements for efficient acquisition with T1 , T2 , and T2∗ weighting. A dictionary-matching approach was used to fit the images to quantitative parameter maps, which in turn were used to create synthetic weighted images with typical clinical contrasts. Dynamic slice-optimized multi-coil shimming with a B0 shim array was used to reduce B0 inhomogeneity and, therefore, image distortion by >50%. Multi-shot EPI was also implemented to minimize distortion and blurring while enabling high in-plane resolution. A low-rank reconstruction approach was used to mitigate errors from shot-to-shot phase variation. RESULTS: The slice-optimized shimming approach was combined with in-plane parallel-imaging acceleration of 4× to enable single-shot EPI with more than eight-fold distortion reduction. The proposed sequence efficiently obtained 40 contrasts across the whole-brain in just over 1 min at 1.2 × 1.2 × 3 mm resolution. The multi-shot variant of the sequence achieved higher in-plane resolution of 1 × 1 × 4 mm with good image quality in 4 min. Derived quantitative maps showed comparable values to conventional mapping methods. CONCLUSION: The approach allows fast whole-brain imaging with quantitative parameter maps and synthetic weighted contrasts. The slice-optimized multi-coil shimming and multi-shot reconstruction approaches result in minimal EPI distortion, giving the sequence the potential to be used in rapid screening applications.