Potential Predictors for Deterioration of Renal Function After Transfusion.

BACKGROUND: Transfusion of packed red blood cells (pRBCs) is still associated with risks. This study aims to determine whether renal function deterioration in the context of individual transfusions in individual patients can be predicted using machine learning. Recipient and donor characteristics linked to increased risk are identified. METHODS: This study was registered at ClinicalTrials.gov (NCT05466370) and was conducted after local ethics committee approval. We evaluated 3366 transfusion episodes from a university hospital between October 31, 2016, and August 31, 2020. Random forest models were tuned and trained via Python auto-sklearn package to predict acute kidney injury (AKI). The models included recipients' and donors' demographic parameters and laboratory values, donor questionnaire results, and the age of the pRBCs. Bootstrapping on the test dataset was used to calculate the means and standard deviations of various performance metrics. RESULTS: AKI as defined by a modified Kidney Disease Improving Global Outcomes (KDIGO) criterion developed after 17.4% transfusion episodes (base rate). AKI could be predicted with an area under the curve of the receiver operating characteristic (AUC-ROC) of 0.73 ± 0.02. The negative (NPV) and positive (PPV) predictive values were 0.90 ± 0.02 and 0.32 ± 0.03, respectively. Feature importance and relative risk analyses revealed that donor features were far less important than recipient features for predicting posttransfusion AKI. CONCLUSIONS: Surprisingly, only the recipients' characteristics played a decisive role in AKI prediction. Based on this result, we speculate that the selection of a specific pRBC may have less influence than recipient characteristics.

Rapid Spin Depolarization in the Layered 2D Ruddlesden-Popper Perovskite (BA)(MA)PbI.

We report temperature-dependent spectroscopy on the layered (n = 4) two-dimensional (2D) Ruddlesden-Popper perovskite (BA)(MA)PbI. Helicity-resolved steady-state photoluminescence (PL) reveals no optical degree of polarization. Time-resolved PL shows a photocarrier lifetime on the order of nanoseconds. From simultaneously recorded time-resolved differential reflectivity (TRΔR) and time-resolved Kerr ellipticity (TRKE), a photocarrier lifetime of a few nanoseconds and a spin relaxation time on the order of picoseconds was found. This stark contrast in lifetimes clearly explains the lack of spin polarization in steady-state PL. While we observe clear temperature-dependent effects on the PL dynamics that can be related to structural dynamics, spin relaxation is nearly T-independent. Our results highlight that spin relaxation in 2D (BA)(MA)PbI occurs at time scales faster than the exciton recombination time, which poses a bottleneck for applications aiming to utilize this degree of freedom.

Using emergency department triage for machine learning-based admission and mortality prediction.

AIMS: Patient admission is a decision relying on sparsely available data. This study aims to provide prediction models for discharge versus admission for ward observation or intensive care, and 30 day-mortality for patients triaged with the Manchester Triage System. METHODS: This is a single-centre, observational, retrospective cohort study from data within ten minutes of patient presentation at the interdisciplinary emergency department of the Kepler University Hospital, Linz, Austria. We trained machine learning models including Random Forests and Neural Networks individually to predict discharge versus ward observation or intensive care admission, and 30 day-mortality. For analysis of the features' relevance, we used permutation feature importance. RESULTS: A total of 58323 adult patients between 1 December 2015 and 31 August 2020 were included. Neural Networks and Random Forests predicted admission to ward observation with an AUC-ROC of 0.842 ±â€…0.00 with the most important features being age and chief complaint. For admission to intensive care, the models had an AUC-ROC of 0.819 ±â€…0.002 with the most important features being the Manchester Triage category and heart rate, and for the outcome 30 day-mortality an AUC-ROC of 0.925 ±â€…0.001. The most important features for the prediction of 30 day-mortality were age and general ward admission. CONCLUSION: Machine learning can provide prediction on discharge versus admission to general wards and intensive care and inform about risk on 30 day-mortality for patients in the emergency department.

Fast-Charging Capability of Thin-Film Prussian Blue Analogue Electrodes for Aqueous Sodium-Ion Batteries.

Prussian blue analogues are considered as promising candidates for aqueous sodium-ion batteries providing a decently high energy density for stationary energy storage. However, suppose the operation of such materials under high-power conditions could be facilitated. In that case, their application might involve fast-response power grid stabilization and enable short-distance urban mobility due to fast re-charging. In this work, sodium nickel hexacyanoferrate thin-film electrodes are synthesized via a facile electrochemical deposition approach to form a model system for a robust investigation. Their fast-charging capability is systematically elaborated with regard to the electroactive material thickness in comparison to a ″traditional″ composite-type electrode. It is found that quasi-equilibrium kinetics allow extremely fast (dis)charging within a few seconds for sub-micron film thicknesses. Specifically, for a thickness below ≈ 500 nm, 90% of the capacity can be retained at a rate of 60C (1 min for full (dis)charge). A transition toward mass transport control is observed when further increasing the rate, with thicker films being dominated by this mode earlier than thinner films. This can be entirely attributed to the limiting effects of solid-state diffusion of Na+ within the electrode material. By presenting a PBA model cell yielding 25 Wh kg-1 at up to 10 kW kg-1, this work highlights a possible pathway toward the guided design of hybrid battery-supercapacitor systems. Furthermore, open challenges associated with thin-film electrodes are discussed, such as the role of parasitic side reactions, as well as increasing the mass loading.

Evaluation of perivascular fat attenuation with coronary CT angiography in cardiac transplantation patients: an imaging biomarker candidate for prediction of cardiac mortality and re-transplantation.

OBJECTIVES: In cardiac transplant recipients, non-invasive allograft surveillance for identifying patients at risk for graft failure remains challenging. The fat attenuation index (FAI) of the perivascular adipose tissue in coronary computed tomography angiography (CCTA) predicts outcomes in coronary artery disease in non-transplanted hearts; however, it has not been evaluated in cardiac transplant patients. METHODS: We followed 39 cardiac transplant patients with two or more CCTAs obtained between 2010 and 2021. We performed FAI measurements around the proximal 4 cm segments of the left anterior descending (LAD), right coronary artery (RCA), and left circumflex artery (LCx) using a previously validated methodology. The FAI was analyzed at a threshold of - 30 to - 190 Hounsfield units. RESULTS: FAI measurements were completed in 113 CCTAs, obtained on two same-vendor CT models. Within each CCTA, the FAI values between coronary vessels were strongly correlated (RCA and LAD R = 0.67 (p < 0.0001), RCA and LCx R = 0.58 (p < 0.0001), LAD and LCx R = 0.67 (p < 0.0001)). The FAIs of each coronary vessel between the patient's first and last CCTA completed at 120 kV were also correlated (RCA R = 0.73 (p < 0.0001), LAD R = 0.81 (p < 0.0001), LCx R = 0.55 (p = 0.0069). Finally, a high mean FAI value of all three coronary vessels at baseline (mean ≥ - 71 HU) was predictive of cardiac mortality or re-transplantation, however, not predictive of all cause-mortality. CONCLUSION: High baseline FAI values may identify a higher-risk cardiac transplant population; thus, FAI may support the implementation of CCTA in post-transplant surveillance. KEY POINT: • Perivascular fat attenuation measured with coronary CT is feasible in cardiac transplant patients and may predict cardiac mortality or need for re-transplantation.

Detection of Post-COVID-19 Lung Abnormalities: Photon-counting CT versus Same-Day Energy-integrating Detector CT.

Background Photon-counting detector (PCD) CT enables ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after COVID-19. Purpose To compare PCD CT with energy-integrating detector (EID) CT for noninvasive assessment of post-COVID-19 lung abnormalities. Materials and Methods For this prospective study, adult participants with one or more COVID-19-related persisting symptoms (resting or exertional dyspnea, cough, fatigue) underwent same-day EID and PCD CT between April 2022 and June 2022. The 1.0-mm EID CT images and, subsequently, 1.0-, 0.4-, and 0.2-mm PCD CT images were reviewed for the presence of lung abnormalities. Subjective and objective EID and PCD CT image quality were evaluated using a five-point Likert scale (-2 to 2) and lung signal-to-noise ratios (SNRs). Results Twenty participants (mean age, 54 years ± 16 [SD]; 10 men) were included. EID CT showed post-COVID-19 lung abnormalities in 15 of 20 (75%) participants, with a median involvement of 10% of lung volume [IQR, 0%-45%] and 3.5 lobes [IQR, 0-5]. Ground-glass opacities and linear bands (10 of 20 participants [50%] for both) were the most frequent findings at EID CT. PCD CT revealed additional lung abnormalities in 10 of 20 (50%) participants, with the most common being bronchiectasis (10 of 20 [50%]). Subjective image quality was improved for 1.0-mm PCD versus 1.0-mm EID CT images (median, 1; IQR, 1-2; P < .001) and 0.4-mm versus 1.0-mm PCD CT images (median, 1; IQR, 1-1; P < .001) but not for 0.4-mm versus 0.2-mm PCD CT images (median, 0; IQR, 0-0.5; P = .26). PCD CT delivered higher lung SNR versus EID CT for 1.0-mm images (mean difference, 0.53 ± 0.96; P = .03) but lower SNR for 0.4-mm versus 1.0-mm images and 0.2-mm vs 0.4-mm images (-1.52 ± 0.68 [P < .001] and -1.15 ± 0.43 [P < .001], respectively). Conclusion Photon-counting detector CT outperformed energy-integrating detector CT in the visualization of subtle post-COVID-19 lung abnormalities and image quality. © RSNA, 2023 Supplemental material is available for this article.

Improving D-2-hydroxyglutarate MR spectroscopic imaging in mutant isocitrate dehydrogenase glioma patients with multiplexed RF-receive/B0 -shim array coils at 3 T.

MR spectroscopic imaging (MRSI) noninvasively maps the metabolism of human brains. In particular, the imaging of D-2-hydroxyglutarate (2HG) produced by glioma isocitrate dehydrogenase (IDH) mutations has become a key application in neuro-oncology. However, the performance of full field-of-view MRSI is limited by B0 spatial nonuniformity and lipid artifacts from tissues surrounding the brain. Array coils that multiplex RF-receive and B0 -shim electrical currents (AC/DC mixing) over the same conductive loops provide many degrees of freedom to improve B0 uniformity and reduce lipid artifacts. AC/DC coils are highly efficient due to compact design, requiring low shim currents (<2 A) that can be switched fast (0.5 ms) with high interscan reproducibility (10% coefficient of variation for repeat measurements). We measured four tumor patients and five volunteers at 3 T and show that using AC/DC coils in addition to the vendor-provided second-order spherical harmonics shim provides 19% narrower spectral linewidth, 6% higher SNR, and 23% less lipid content for unrestricted field-of-view MRSI, compared with the vendor-provided shim alone. We demonstrate that improvement in MRSI data quality led to 2HG maps with higher contrast-to-noise ratio for tumors that coincide better with the FLAIR-enhancing lesions in mutant IDH glioma patients. Smaller Cramér-Rao lower bounds for 2HG quantification are obtained in tumors by AC/DC shim, corroborating with simulations that predicted improved accuracy and precision for narrower linewidths. AC/DC coils can be used synergistically with optimized acquisition schemes to improve metabolic imaging for precision oncology of glioma patients. Furthermore, this methodology has broad applicability to other neurological disorders and neuroscience.

Manganese doping for enhanced magnetic brightening and circular polarization control of dark excitons in paramagnetic layered hybrid metal-halide perovskites.

Materials combining semiconductor functionalities with spin control are desired for the advancement of quantum technologies. Here, we study the magneto-optical properties of novel paramagnetic Ruddlesden-Popper hybrid perovskites Mn:(PEA)2PbI4 (PEA = phenethylammonium) and report magnetically brightened excitonic luminescence with strong circular polarization from the interaction with isolated Mn2+ ions. Using a combination of superconducting quantum interference device (SQUID) magnetometry, magneto-absorption and transient optical spectroscopy, we find that a dark exciton population is brightened by state mixing with the bright excitons in the presence of a magnetic field. Unexpectedly, the circular polarization of the dark exciton luminescence follows the Brillouin-shaped magnetization with a saturation polarization of 13% at 4 K and 6 T. From high-field transient magneto-luminescence we attribute our observations to spin-dependent exciton dynamics at early times after excitation, with first indications for a Mn-mediated spin-flip process. Our findings demonstrate manganese doping as a powerful approach to control excitonic spin physics in Ruddlesden-Popper perovskites, which will stimulate research on this highly tuneable material platform with promise for tailored interactions between magnetic moments and excitonic states.

Real-time motion and retrospective coil sensitivity correction for CEST using volumetric navigators (vNavs) at 7T.

PURPOSE: To explore the impact of temporal motion-induced coil sensitivity changes on CEST-MRI at 7T and its correction using interleaved volumetric EPI navigators, which are applied for real-time motion correction. METHODS: Five healthy volunteers were scanned via CEST. A 4-fold correction pipeline allowed the mitigation of (1) motion, (2) motion-induced coil sensitivity variations, ΔB1- , (3) motion-induced static magnetic field inhomogeneities, ΔB0 , and (4) spatially varying transmit RF field fluctuations, ΔB1+ . Four CEST measurements were performed per session. For the first 2, motion correction was turned OFF and then ON in absence of voluntary motion, whereas in the other 2 controlled head rotations were performed. During post-processing ΔB1- was removed additionally for the motion-corrected cases, resulting in a total of 6 scenarios to be compared. In all cases, retrospective ∆B0 and - ΔB1+ corrections were performed to compute artifact-free magnetization transfer ratio maps with asymmetric analysis (MTRasym ). RESULTS: Dynamic ΔB1- correction successfully mitigated signal deviations caused by head motion. In 2 frontal lobe regions of volunteer 4, induced relative signal errors of 10.9% and 3.9% were reduced to 1.1% and 1.0% after correction. In the right frontal lobe, the motion-corrected MTRasym contrast deviated 0.92%, 1.21%, and 2.97% relative to the static case for Δω = 1, 2, 3 ± 0.25 ppm. The additional application of ΔB1- correction reduced these deviations to 0.10%, 0.14%, and 0.42%. The fully corrected MTRasym values were highly consistent between measurements with and without intended head rotations. CONCLUSION: Temporal ΔB1- cause significant CEST quantification bias. The presented correction pipeline including the proposed retrospective ΔB1- correction significantly reduced motion-related artifacts on CEST-MRI.

Whole-Slab 3D MR Spectroscopic Imaging of the Human Brain With Spiral-Out-In Sampling at 7T.

BACKGROUND: Metabolic imaging using proton magnetic resonance spectroscopic imaging (MRSI) has increased the sensitivity and spectral resolution at field strengths of ≥7T. Compared to the conventional Cartesian-based spectroscopic imaging, spiral trajectories enable faster data collection, promising the clinical translation of whole-brain MRSI. Technical considerations at 7T, however, lead to a suboptimal sampling efficiency for the spiral-out (SO) acquisitions, as a significant portion of the trajectory consists of rewinders. PURPOSE: To develop and implement a spiral-out-in (SOI) trajectory for sampling of whole-brain MRSI at 7T. We hypothesized that SOI will improve the signal-to-noise ratio (SNR) of metabolite maps due to a more efficient acquisition. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Five healthy volunteers (28-38 years, three females) and a phantom. FIELD STRENGTH/SEQUENCE: Navigated adiabatic spin-echo spiral 3D MRSI at 7T. ASSESSMENT: A 3D stack of SOI trajectories was incorporated into an adiabatic spin-echo MRSI sequence with real-time motion and shim correction. Metabolite spectral fitting, SNR, and Cramér-Rao lower bound (CRLB) were obtained. We compared the signal intensity and CRLB of three metabolites of tNAA, tCr, and tCho. Peak SNR (PSNR), structure similarity index (SSIM), and signal-to-artifact ratio were evaluated on water maps. STATISTICAL TESTS: The nonparametric Mann-Whitney U-test was used for statistical testing. RESULTS: Compared to SO, the SOI trajectory: 1) increased the k-space sampling efficiency by 23%; 2) is less demanding for the gradient hardware, requiring 36% lower Gmax and 26% lower Smax ; 3) increased PSNR of water maps by 4.94 dB (P = 0.0006); 4) resulted in a 29% higher SNR (P = 0.003) and lower CRLB by 26-35% (P = 0.02, tNAA), 35-55% (P = 0.03, tCr), and 22-23% (P = 0.04, tCho), which increased the number of well-fitted voxels (eg, for tCr by 11%, P = 0.03). SOI did not significantly change the signal-to-artifact ratio and SSIM (P = 0.65) compared to SO. DATA CONCLUSION: SOI provided more efficient MRSI at 7T compared to SO, which improved the data quality and metabolite quantification. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Effects of different macromolecular models on reproducibility of FID-MRSI at 7T.

PURPOSE: A properly characterized macromolecular (MM) contribution is essential for accurate metabolite quantification in FID-MRSI. MM information can be included into the fitting model as a single component or parameterized and included over several individual MM resonances, which adds flexibility when pathologic changes are present but is prone to potential overfitting. This study investigates the effects of different MM models on MRSI reproducibility. METHODS: Clinically feasible, high-resolution FID-MRSI data were collected in ~5 min at 7 Tesla from 10 healthy volunteers and quantified via LCModel (version 6.3) with 3 basis sets, each with a different approach for how the MM signal was handled: averaged measured whole spectrum (full MM), 9 parameterized components (param MM) with soft constraints to avoid overparameterization, or without any MM information included in the fitting prior knowledge. The test-retest reproducibility of MRSI scans was assessed voxel-wise using metabolite coefficients of variation and intraclass correlation coefficients and compared between the basis sets. Correlations of concentration estimates were investigated for the param MM fitting model. RESULTS: The full MM model provided the most reproducible quantification of total NAA, total Cho, myo-inositol, and glutamate + glutamine ratios to total Cr (coefficients of variations ≤ 8%, intraclass correlation coefficients ≥ 0.76). Using the param MM model resulted in slightly lower reproducibility (up to +3% higher coefficients of variations, up to -0.1 decreased intraclass correlation coefficients). The quantification of the parameterized macromolecules did not affect quantification of the overlapping metabolites. CONCLUSION: Clinically feasible FID-MRSI with an experimentally acquired MM spectrum included in prior knowledge provides highly reproducible quantification for the most common neurometabolites in healthy volunteers. Parameterization of the MM spectrum may be preferred as a compromise between quantification accuracy and reproducibility when the MM content is expected to be pathologically altered.

Clinical High-Resolution 3D-MR Spectroscopic Imaging of the Human Brain at 7 T.

OBJECTIVES: Available clinical magnetic resonance spectroscopic imaging (MRSI) sequences are hampered by long scan times, low spatial resolution, strong field inhomogeneities, limited volume coverage, and low signal-to-noise ratio. High-resolution, whole-brain mapping of more metabolites than just N-acetylaspartate, choline, and creatine within clinically attractive scan times is urgently needed for clinical applications. The aim is therefore to develop a free induction decay (FID) MRSI sequence with rapid concentric ring trajectory (CRT) encoding for 7 T and demonstrate its clinical feasibility for mapping the whole cerebrum of healthy volunteers and patients. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Time-efficient, 3-dimensional encoding of an ellipsoidal k-space by in-plane CRT and through-plane phase encoding was integrated into an FID-MRSI sequence. To reduce scan times further, repetition times were shortened, and variable temporal interleaves were applied. Measurements with different matrix sizes were performed to validate the CRT encoding in a resolution phantom. One multiple sclerosis patient, 1 glioma patient, and 6 healthy volunteers were prospectively measured. For the healthy volunteers, brain segmentation was performed to quantify median metabolic ratios, Cramér-Rao lower bounds (CRLBs), signal-to-noise ratios, linewidths, and brain coverage among all measured matrix sizes ranging from a 32 × 32 × 31 matrix with 6.9 × 6.9 × 4.2 mm nominal voxel size acquired in ~3 minutes to an 80 × 80 × 47 matrix with 2.7 × 2.7 × 2.7 mm nominal voxel size in ~15 minutes for different brain regions. RESULTS: Phantom structures with diameters down to 3 to 4 mm were visible. In vivo MRSI provided high spectral quality (median signal-to-noise ratios, >6.3 and linewidths, <0.082 ppm) and fitting quality. Cramér-Rao lower bounds were ranging from less than 22% for glutamine (highest CRLB in subcortical gray matter) to less than 9.5% for N-acetylaspartate for the 80 × 80 × 47 matrix (highest CRLB in the temporal lobe). This enabled reliable mapping of up to 8 metabolites (N-acetylaspartate, N-acetylaspartyl glutamate, total creatine, glutamine, glutamate, total choline, myo-inositol, glycine) and macromolecules for all resolutions. Coverage of the whole cerebrum allowed visualization of the full extent of diffuse and local multiple sclerosis-related neurochemical changes (eg, up to 100% increased myo-inositol). Three-dimensional brain tumor metabolic maps provided valuable information beyond that of single-slice MRSI, with up to 200% higher choline, up to 100% increased glutamine, and increased glycine in tumor tissue. CONCLUSIONS: Seven Tesla FID-MRSI with time-efficient CRT readouts offers clinically attractive acquisition protocols tailored either for speed or for the investigation of small pathologic details and low-abundant metabolites. This can complement clinical MR studies of various brain disorders. Significant metabolic anomalies were demonstrated in a multiple sclerosis and a glioma patient for myo-inositol, glutamine, total choline, glycine, and N-acetylaspartate concentrations.

Intra-session and inter-subject variability of 3D-FID-MRSI using single-echo volumetric EPI navigators at 3T.

PURPOSE: In this study, we demonstrate the first combination of 3D FID proton MRSI and spatial encoding via concentric-ring trajectories (CRTs) at 3T. FID-MRSI has many benefits including high detection sensitivity, in particular for J-coupled metabolites (e.g., glutamate/glutamine). This makes it highly attractive, not only for clinical, but also for, potentially, functional MRSI. However, this requires excellent reliability and temporal stability. We have, therefore, augmented this 3D-FID-MRSI sequence with single-echo, imaging-based volumetric navigators (se-vNavs) for real-time motion/shim-correction (SHMOCO), which is 2× quicker than the original double-echo navigators (de-vNavs), hence allowing more efficient integration also in short-TR sequences. METHODS: The tracking accuracy (position and B0 -field) of our proposed se-vNavs was compared to the original de-vNavs in phantoms (rest and translation) and in vivo (voluntary head rotation). Finally, the intra-session stability of a 5:40 min 3D-FID-MRSI scan was evaluated with SHMOCO and no correction (NOCO) in 5 resting subjects. Intra/inter-subject coefficients of variation (CV) and intra-class correlations (ICC) over the whole 3D volume and in selected regions of interest ROI were assessed. RESULTS: Phantom and in vivo scans showed highly consistent tracking performance for se-vNavs compared to the original de-vNavs, but lower frequency drift. Up to ~30% better intra-subject CVs were obtained for SHMOCO (P < 0.05), with values of 9.3/6.9/6.5/7.8% over the full VOI for Glx/tNAA/tCho/m-Ins ratios to tCr. ICCs were good-to-high (91% for Glx/tCr in motor cortex), whereas the inter-subject variability was ~11-19%. CONCLUSION: Real-time motion/shim corrected 3D-FID-MRSI with time-efficient CRT-sampling at 3T allows reliable, high-resolution metabolic imaging that is fast enough for clinical use and even, potentially, for functional MRSI.

Hippocampal GABA levels correlate with retrieval performance in an associative learning paradigm.

Neural plasticity is a complex process dependent on neurochemical underpinnings. Next to the glutamatergic system which contributes to memory formation via long-term potentiation (LTP) and long-term depression (LTD), the main inhibitory neurotransmitter, GABA is crucially involved in neuroplastic processes. Hence, we investigated changes in glutamate and GABA levels in the brain in healthy participants performing an associative learning paradigm. Twenty healthy participants (10 female, 25 ±â€¯5 years) underwent paired multi-voxel magnetic resonance spectroscopy imaging before and after completing 21 days of a facial associative learning paradigm in a longitudinal study design. Changes of GABA and glutamate were compared to retrieval success in the hippocampus, insula and thalamus. No changes in GABA and glutamate concentration were found after 21 days of associative learning. However, baseline hippocampal GABA levels were significantly correlated with initial retrieval success (pcor = 0.013, r = 0.690). In contrast to the thalamus and insula (pcor>0.1), higher baseline GABA levels in the hippocampus were associated with better retrieval performance in an associative learning paradigm. Therefore, our findings support the importance of hippocampal GABA levels in memory formation in the human brain in vivo.

Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds.

Current reconstruction methods of the laryngotracheal segment fail to replace the complex functions of the human larynx. Bioengineering approaches to reconstruction have been limited by the complex tissue compartmentation of the larynx. We attempted to overcome this limitation by bioengineering laryngeal grafts from decellularized canine laryngeal scaffolds recellularized with human primary cells under one uniform culture medium condition. First, we developed laryngeal scaffolds which were generated by detergent perfusion-decellularization over 9 days and preserved their glycosaminoglycan content and biomechanical properties of a native larynx. After subcutaneous implantations in rats for 14 days, the scaffolds did not elicit a CD3 lymphocyte response. We then developed a uniform culture medium that strengthened the endothelial barrier over 5 days after an initial growth phase. Simultaneously, this culture medium supported airway epithelial cell and skeletal myoblast growth while maintaining their full differentiation and maturation potential. We then applied the uniform culture medium composition to whole laryngeal scaffolds seeded with endothelial cells from both carotid arteries and external jugular veins and generated reendothelialized arterial and venous vascular beds. Under the same culture medium, we bioengineered epithelial monolayers onto laryngeal mucosa and repopulated intrinsic laryngeal muscle. We were then able to demonstrate early muscle formation in an intramuscular transplantation model in immunodeficient mice. We supported formation of three humanized laryngeal tissue compartments under one uniform culture condition, possibly a key factor in developing complex, multicellular, ready-to-transplant tissue grafts. Impact Statement For patients undergoing laryngectomy, no reconstruction methods are available to restore the complex functions of the human larynx. The first promising preclinical results have been achieved with the use of biological scaffolds fabricated from decellularized tissue. However, the complexity of laryngeal tissue composition remains a hurdle to create functional viable grafts, since previously each cell type requires tailored culture conditions. In this study, we report the de novo formation of three humanized laryngeal tissue compartments under one uniform culture condition, a possible keystone in creating vital composite tissue grafts for laryngeal regeneration.

Non-Cartesian GRAPPA and coil combination using interleaved calibration data - application to concentric-ring MRSI of the human brain at 7T.

PURPOSE: Proton MR spectroscopic imaging (MRSI) benefits from B0 ≥ 7T and multichannel receive coils, promising substantial resolution improvements. However, MRSI acquisition with high spatial resolution requires efficient acceleration and coil combination. To speed up the already-fast sampling via concentric rings, we implemented additional, non-Cartesian, hybrid through-time/through-k-space (tt/tk)-generalized autocalibrating partially parallel acquisition (GRAPPA). A new multipurpose interleaved calibration scan (interleaved MUSICAL) acquires reference data for both coil combination and PI. This renders the reconstruction process (especially PI) less sensitive to instabilities. METHODS: Six healthy volunteers were scanned at 7T. Three calibration datasets for coil combination and PI were recorded: a) iMUSICAL, b) static MUSICAL as prescan, c) moved MUSICAL as prescan with misaligned head position. The coil combination performance, including motion sensitivity, of iMUSICAL was compared to MUSICAL for single-slice free induction decay (FID)-MRSI. Through-time/through-k-space-GRAPPA with constant/variable-density undersampling was evaluated on the same data, comparing the three calibration datasets. Additionally, the proposed method was successfully applied to 3D whole-brain FID-MRSI. RESULTS: Using iMUSICAL for coil combination yielded the highest signal-to-noise ratio (SNR) (+9%) and lowest Cramer-Rao lower bounds (CRLBs) (-6%) compared to both MUSICAL approaches, with similar metabolic map quality. Also, excellent mean g-factors of 1.07 and low residual lipid aliasing were obtained when using iMUSICAL as calibration data for two-fold, variable-density undersampling, while significantly degraded metabolic maps were obtained using the misaligned MUSICAL calibration data. CONCLUSION: Through-time/through-k-space-GRAPPA can accelerate already time-efficient non-Cartesian spatial-spectral 2D/3D-MRSI encoding even further. Particularly promising results have been achieved using iMUSICAL as a robust, interleaved multipurpose calibration for MRSI reconstruction, without extra calibration prescan.

The influence of spatial resolution on the spectral quality and quantification accuracy of whole-brain MRSI at 1.5T, 3T, 7T, and 9.4T.

PURPOSE: Inhomogeneities in the static magnetic field (B0 ) deteriorate MRSI data quality by lowering the spectral resolution and SNR. MRSI with low spatial resolution is also prone to lipid bleeding. These problems are increasingly problematic at ultra-high fields. An approach to tackling these challenges independent of B0 -shim hardware is to increase the spatial resolution. Therefore, we investigated the effect of improved spatial resolution on spectral quality and quantification at 4 field strengths. METHODS: Whole-brain MRSI data was simulated for 3 spatial resolutions and 4 B0 s based on experimentally acquired MRI data and simulated free induction decay signals of metabolites and lipids. To compare the spectral quality and quantification, we derived SNR normalized to the voxel size (nSNR), linewidth and metabolite concentration ratios, their Cramer-Rao-lower-bounds (CRLBs), and the absolute percentage error (APE) of estimated concentrations compared to the gold standard for the whole-brain and 8 brain regions. RESULTS: At 7T, we found up to a 3.4-fold improved nSNR (in the frontal lobe) and a 2.8-fold reduced linewidth (in the temporal lobe) for 1 cm3 versus 0.25 cm3 resolution. This effect was much more pronounced at higher and less homogenous B0 (1.6-fold improved nSNR and 1.8-fold improved linewidth in the parietal lobe at 3T). This had direct implications for quantification: the volume of reliably quantified spectra increased with resolution by 1.2-fold and 1.5-fold (when thresholded by CRLBs or APE, respectively). CONCLUSION: MRSI data quality benefits from increased spatial resolution particularly at higher B0 , and leads to more reliable metabolite quantification. In conjunction with the development of better B0 shimming hardware, this will enable robust whole-brain MRSI at ultra-high field.

Automated ROI-Based Labeling for Multi-Voxel Magnetic Resonance Spectroscopy Data Using FreeSurfer.

Purpose: Advanced analysis methods for multi-voxel magnetic resonance spectroscopy (MRS) are crucial for neurotransmitter quantification, especially for neurotransmitters showing different distributions across tissue types. So far, only a handful of studies have used region of interest (ROI)-based labeling approaches for multi-voxel MRS data. Hence, this study aims to provide an automated ROI-based labeling tool for 3D-multi-voxel MRS data. Methods: MRS data, for automated ROI-based labeling, was acquired in two different spatial resolutions using a spiral-encoded, LASER-localized 3D-MRS imaging sequence with and without MEGA-editing. To calculate the mean metabolite distribution within selected ROIs, masks of individual brain regions were extracted from structural T1-weighted images using FreeSurfer. For reliability testing of automated labeling a comparison to manual labeling and single voxel selection approaches was performed for six different subcortical regions. Results: Automated ROI-based labeling showed high consistency [intra-class correlation coefficient (ICC) > 0.8] for all regions compared to manual labeling. Higher variation was shown when selected voxels, chosen from a multi-voxel grid, uncorrected for voxel composition, were compared to labeling methods using spatial averaging based on anatomical features within gray matter (GM) volumes. Conclusion: We provide an automated ROI-based analysis approach for various types of 3D-multi-voxel MRS data, which dramatically reduces hands-on time compared to manual labeling without any possible inter-rater bias.

A comparison of static and dynamic ∆B0 mapping methods for correction of CEST MRI in the presence of temporal B0 field variations.

PURPOSE: To assess the performance, in the presence of scanner instabilities, of three dynamic correction methods which integrate ∆B0 mapping into the chemical exchange saturation transfer (CEST) measurement and three established static ∆B0 -correction approaches. METHODS: A homogeneous phantom and five healthy volunteers were scanned with a CEST sequence at 7 T. The in vivo measurements were performed twice: first with unaltered system frequency and again applying frequency shifts during the CEST acquisition. In all cases, retrospective voxel-wise ∆B0 -correction was performed using one intrinsic and two extrinsic [prescans with dual-echo gradient-echo and water saturation shift referencing (WASSR)] static approaches. These were compared with two intrinsic [using phase data directly generated by single-echo or double-echo GRE (gradient-echo) CEST readout (CEST-GRE-2TE)] and one extrinsic [phase from interleaved dual-echo EPI (echo planar imaging) navigator (NAV-EPI-2TE)] dynamic ∆B0 -correction approaches [allowing correction of each Z-spectral point before magnetization transfer ratio asymmetry (MTRasym) analysis]. RESULTS: All three dynamic methods successfully mapped the induced drift. The intrinsic approaches were affected by the CEST labeling near water (∆ω < |0.3| ppm). The MTRasym contrast was distorted by the frequency drift in the brain by up to 0.21%/Hz when static ∆B0 -corrections were applied, whereas the dynamic ∆B0 corrections reduced this to <0.01%/Hz without the need of external scans. The CEST-GRE-2TE and NAV-EPI-2TE resulted in highly consistent MTRasym values with/without drift for all subjects. CONCLUSION: Reliable correction of scanner instabilities is essential to establish clinical CEST MRI. The three dynamic approaches presented improved the ∆B0 -correction performance significantly in the presence of frequency drift compared to established static methods. Among them, the self-corrected CEST-GRE-2TE was the most accurate and straightforward to implement.

Biofabrication of a vascularized islet organ for type 1 diabetes.

Islet transplantation is superior to extrinsic insulin supplementation in the treating severe Type 1 diabetes. However, its efficiency and longevity are limited by substantial islet loss post-transplantation due to lack of engraftment and vascular supply. To overcome these limitations, we developed a novel approach to bio-fabricate functional, vascularized islet organs (VIOs) ex vivo. We endothelialized acellular lung matrixes to provide a biocompatible multicompartment scaffold with an intact hierarchical vascular tree as a backbone for islet engraftment. Over seven days of culture, islets anatomically and functionally integrated into the surrounding bio-engineered vasculature, generating a functional perfusable endocrine organ. When exposed to supra-physiologic arterial glucose levels in vivo and ex vivo, mature VIOs responded with a physiologic insulin release from the vein and provided more efficient reduction of hyperglycemia compared to intraportally transplanted fresh islets. In long-term transplants in diabetic mice, subcutaneously implanted VIOs achieved normoglycemia significantly faster and more efficiently compared to islets that were transplanted in deviceless fashion. We conclude that ex vivo bio-fabrication of VIOs enables islet engraftment and vascularization before transplantation, and thereby helps to overcome limited islet survival and function observed in conventional islet transplantation. Given recent progress in stem cells, this technology may enable assembly of functional personalized endocrine organs.