Double Inversion Research Articles

Double inversion recovery MRI versus contrast-enhanced MRI for evaluation of knee synovitis in juvenile idiopathic arthritis

BackgroundDouble inversion recovery (DIR) MRI has the potential to accentuate the synovium without using contrast agents, as it allows simultaneous signal suppression of fluid and fat. The purpose of this study was (1) to compare DIR MRI to conventional contrast-enhanced (CE) MRI for delineation of the synovium in the knee in children with juvenile idiopathic arthritis (JIA) and (2) to assess the agreement between DIR MRI and CE-MRI regarding maximal synovial thickness measurements.ResultsIn this prospective study, 26 children with JIA who consecutively underwent 3.0-T knee MRI between January 2018 and January 2021 were included (presence of knee arthritis: 13 [50%]; median age: 14 years [interquartile range [IQR]: 11–17]; 14 girls). Median confidence to depict the synovium (0–100 mm visual analogue scale; scored by 2 readers [consensus based]) was 88 (IQR: 79–97) for DIR MRI versus 100 (IQR: 100–100) for CE-MRI (p value = < .001). Maximal synovial thickness per child (millimeters; scored by 4 individual readers) on DIR MRI was greater (p value = < .001) in the children with knee arthritis (2.4 mm [IQR: 2.1–3.1]) than in those without knee arthritis (1.4 mm [IQR: 1.0–1.6]). Good inter-technique agreement for maximal synovial thickness per child was observed (rs = 0.93 [p value = < .001]; inter-reader reliability: ICC DIR MRI = 0.87 [p value = < .001], ICC CE-MRI = 0.90 [p value = < .001]).ConclusionDIR MRI adequately delineated the synovium in the knee of children with JIA and enabled synovial thickness measurement similar to that of CE-MRI. Our results demonstrate that DIR MRI should be considered as a child-friendly alternative to CE-MRI for evaluation of synovitis in children with (suspected) JIA.

Fast bound and pore water mapping of cortical bone witharbitrary slice oriented two-dimensional ultra-short echo time.

Extend fast, two-dimensional (2D) methods of bound and pore water mapping in bone to arbitrary slice orientation. To correct for slice profile artifacts caused by gradient errors of half pulse 2D ultra-short echo time (UTE), we developed a library of predistorted gradient waveforms that can be used to interpolate optimized gradient waveforms for 2D UTE slice selection. We also developed a method to estimate and correct for a bulk phase difference between the two half pulse excitations used for 2D UTE signal excitation. Bound water images were acquired in three healthy subjects with adiabatic inversion recovery prepared 2D UTE, while pore water images were acquired after short-T2 signals were suppressed with double adiabatic inversion recovery preparation. The repeatability of bound and pore water imaging with 2D UTE was tested by repeating acquisitions after repositioning. The library-based interpolation of optimized slice select gradient waveforms combined with the method to estimate bulk phase between two excitations provided compact slice profiles for half pulse excited 2D UTE. Quantitative bound and pore water values were highly repeatable-the pooled SD of bound water across all three subjects was 0.38 mol H/L, while pooled SD of pore water was 0.30 mol H/L. Fast, quantitative, 2D UTE-based bound and pore water images can be acquired at arbitrary oblique orientations after correcting for errors in the slice select gradient waveform and bulk phase shift between the two half acquisitions.

Anatomical and Technical Preparations of the Human Brain for White Matter Fibers Dissection with Electromagnetic Neuronavigation Assistance Technical Nuances for Application

Klinger's fiber dissection technique is widely used for studying the anatomy of white matter. Herein, we present a technical description of Klinger's proposed fiber dissection algorithm with neuronavigation assistance which allows for a more accurate determination of the projection of association fibers. An anatomical study was conducted on 8 hemispheres of the human brain, prepared according to the Klingler fiber dissection technique. In all the cases, a frameless electromagnetic navigation system was used. For each anatomical specimen, an individualized support device was three-dimensional -printed and placed it into the magnetic resonance imaging (MRI) gantry. MRI study of each anatomical specimen was performed using a specific protocol that enabled a subsequent three-dimensional visualization of the anatomical structures as follows: FSPGR (Fast SPoiled Gradient Recalled echo) BRAVO (BRAin VOlume Imaging), T2 CUBE, FLAIR (FLuid Attenuated Inversion Recovery) CUBE, CUBE DIR (double inversion recovery) WHITE MATTER, and CUBE DIR GRAY MATTER. The average time required to register an anatomical specimen in the navigation system was 7minutes 28seconds. In all of the 8 cases, the anatomical structures were correctly identified using neuronavigation. Moreover, the choice of MRI mode depends on the purpose of the study and the region of interest in the brain. Electromagnetic navigation is an accurate and useful technique. It allows the researcher the ability to virtually project the association fibers and their cortico-cortical terminations to the surface of the brain, even at the final stages of dissection when the superficial structures are removed. To obtain accurate targeting, it is important to use the appropriate neuronavigation protocol.

Unremovable linked nodal structures protected by crystalline symmetries in stacked bilayer graphene with Kekulé texture

Linking structure is a new concept characterizing topological semimetals, which indicates the interweaving of gap-closing nodes at the Fermi energy ($E_F$) with other nodes below $E_F$. As the number of linked nodes can be changed only via pair-creation or pair-annihilation, a linked node is more stable and robust than ordinary nodes without linking. Here we propose a new type of a linked nodal structure between a nodal line (nodal surface) at $E_F$ with another nodal line (nodal surface) below $E_F$ in two-dimensional (three-dimensional) spinless fermion systems with $\mathcal{IT}$ symmetry where $\mathcal{I}$ and $\mathcal{T}$ indicate inversion and time-reversal symmetries, respectively. Because of additional chiral and rotational symmetries, in our system, a double band inversion creates a pair of linked nodes carrying the same topological charges, thus the pair are unremovable via a Lifshiftz transition, which is clearly distinct from the cases of the linked nodes reported previously. A realistic tight binding model and effective theory are developed for such a linking structure. Also, using density functional theory calculations, we propose a class of materials, composed of stacked bilayer graphene with Kekul\'{e} texture, as a candidate system hosting the new type of the linked nodal structure.

Comparison of 3D Double Inversion Recovery (DIR) versus 3D Fluid Attenuated Inversion Recovery (FLAIR) in precise diagnosis of acute optic neuritis

BackgroundThe small size, intraorbital fat, perioptic CSF sheath and air-bone interface pose challenges to optic nerve imaging in cases of acute optic neuritis. The study is intended to compare the diagnostic accuracy of 3-dimensional Fluid Attenuation Inversion Recovery (3D FLAIR) and 3-dimensional Double Inversion Recovery (3D DIR) in cases of acute optic neuritis (AON). MethodsCases of AON with visual evoked potentials (VEP) abnormality were recruited and compared with controls. Imaging protocol incorporated 3D FLAIR and 3D DIR to routine sequences. The optic nerve signal was evaluated for hyperintensity across three segments viz, intraorbital, prechiasmatic, and optic-chiasm segments. The inter-modality agreement, odds ratio, receiver operator characteristics (ROC) curve, Signal intensity ratio (SIR) and interobserver agreement (between two experienced neuroradiologists) was compared between the sequences. ResultsGood Intermodality agreement (IMA) was found in the PC segment (ICC: 0.748, p < 0.001) in the Likert scale. In a binary scale of analysis (signal Normal vs abnormal) Kappa was highest for the PC segment (0.525, p < 0.001). The 3D-DIR sequence had an overall higher odds ratio (OR) of detecting abnormality compared to 3D-FLAIR. OR was highest for 3D DIR in the Orbital segment (OR: 3.64, P-value < 0.001) and for FLAIR in the chiasmal segment (OR 2.25, P = 0.007) for predicting optic neuritis. The area under the ROC curve for 3-D DIR was larger across all the segments (0.8 vs 0.623, p < 0.001). The Area under ROC for signal intensity ratio was higher for 3D-DIR(0.844 vs 0.704, p = 0.004) Conclusion3D DIR, under its unique contrast-generating scheme, demonstrates a greater diagnostic accuracy and offers confidence in the diagnosis of AON lesions when compared to 3D FLAIR.

Relation between retina, cognition and brain volumes in MS: a consequence of asymptomatic optic nerve lesions.

Asymptomatic optic nerve lesions are frequent in multiple sclerosis (MS) and their impact on cognition and/or brain volume has never been taken into account. We used the data from the cross-sectional Visual Ways in MS (VWIMS) study including relapsing remitting MS. All patients underwent brain and optic nerve Magnetic Resonance Imaging (MRI) including Double Inversion Recuperation (DIR) sequence, retinal OCT, and cognitive evaluation with the Brief International Cognitive Assessment in MS (BICAMS). We measured the association between OCT findings (thickness/volume of retinal layers) and extra-visual parameters (cerebral volumes and BICAMS scores) in optic nerves with and/or without the presence of DIR asymptomatic optic nerve hypersignal. Between March and December 2017, we included 98 patients. Two patients were excluded. Over the 192 eyes, 73 had at least one clinical history of optic neuritis (ON-eyes) whereas 119 were asymptomatic (NON-eyes). Among the 119 NON-eyes, 58 had 3D-DIR optic nerve hypersignal (48.7%). We confirmed significant associations between some retinal OCT measures and some extra-visual parameters (cerebral volumes, cognitive scores) in NON-eyes. Unexpectedly, these associations were found when an asymptomatic optic nerve DIR-hypersignal was present on MRI, but not when it was absent. Our study showed a relation between OCT measures and extra-visual parameters in NON-eyes MS patients. As a confusion factor, asymptomatic optic nerve lesions may be the explanation of the relation between OCT measures and extra-visual parameters. Retinal OCT seems to be far more a "window over the optic nerve" than a "window over the brain".

Efficient Preparation of 2‐SAc‐Glycosyl Donors and Investigation of Their Application in the Synthesis of 2‐Deoxyglycosides

AbstractIn this study, we have developed efficient strategies for the synthesis of glycosyl donors with 2‐thioacetyl (SAc) groups in order to synthesize 2‐deoxysugars with exclusive α/β‐configuration. Starting from free methyl glycosides, four methyl 2‐SAc glycosides were synthesized with high efficiency mainly through the double serial inversion strategy, and further turned into four corresponding 1‐OAc, 2‐SAc α‐glycosyl donors (manno‐, gluco‐, galacto‐ and talo‐types) and four corresponding 1‐STol, 2‐SAc 1,2‐cis‐glycosyl donors (manno‐, gluco‐, galacto‐ and talo‐types). Glycosylation of the 1‐OAc, 2‐SAc donors and further 2‐deoxysugar synthesis have also been investigated in this study.

Improved detection of multiple sclerosis lesions with T2-prepared double inversion recovery at 3T.

Background and PurposeDouble inversion recovery (DIR) imaging is used in multiple sclerosis (MS) clinical protocols to improve the detection of cortical and juxtacortical gray matter lesions by nulling confounding signals originating from the cerebrospinal fluid and white matter. Achieving a high isotropic spatial resolution, to depict the neocortex and its typically small lesions, is challenged by the reduced signal‐to‐noise ratio (SNR) determined by multiple tissue signal nulling. Here, we evaluate both conventional and optimized DIR implementations to improve tissue contrast (TC), SNR, and MS lesion conspicuity.MethodsDIR images were obtained from MS patients and healthy controls using both conventional and prototype implementations featuring a T2‐preparation module (T2P), to improve SNR and TC, as well as an image reconstruction routine with iterative denoising (ID). We obtained quantitative measures of SNR and TC, and evaluated the visibility of MS cortical, cervical cord, and optic nerve lesions in the different DIR images.ResultsDIR implementations adopting T2P and ID enabled improving the SNR and TC of conventional DIR. In MS patients, 34% of cortical, optic nerve, and cervical cord lesions were visible only in DIR images acquired with T2P, and not in conventional DIR images. In the studied cases, image reconstruction with ID did not improve lesion conspicuity.ConclusionsDIR with T2P should be preferred to conventional DIR imaging in protocols studying MS patients, as it improves SNR and TC and determines an improvement in cortical, optic nerve, and cervical cord lesion conspicuity.

Synthesis of Oligosaccharides Containing the S-Galp(α1 → 3)Galp Unit, Glycomimetic of the Epitope Recognized by Lytic Antibodies.

Two important activities take place in the surface of Trypanosoma cruzi, the agent of Chagas disease: the trans-sialidase (TcTS) catalyzes the transfer of sialic acid from the host glycoconjugates to the mucin-like glycoproteins from the parasite and the presence of lytic antibodies recognize the epitope α-Galp(1 → 3)-β-Galp(1 → 4)-α-GlcNAcp. This antigenic structure is known to be present in the parasite mucins; however, in order to be substrates of trans-sialidase, some of the galactose residues should be in the β-Galp configuration. To study the interaction between both activities, it is important to count the synthetic structures as well as the structural-related glycomimetics. With this purpose, we addressed the synthesis of a trisaccharide and two isomeric tetrasaccharides containing the 1-S-α-Galp(1 → 3)-β-Galp motif, the thio analog of the epitope recognized by lytic antibodies. Starting with a common lactose precursor, the sulfur function was incorporated by double inversion of the configuration of the galactose residue that was further glycosylated using different activated donors. Both tetrasaccharides were good acceptors of sialic acid in the reaction catalyzed by TcTS, as determined by high-performance anion exchange chromatography.

Congenitally Corrected Transposition of Great arteries with AV block -cohabitation of structural and electrical cardiac abnormality: a case report

Congenitally Corrected Transposition of Great Arteries (c-TGA) is an anomaly with atrioventricular and ventriculoarterial discordance where left atrium connects to right ventricle and right atrium to left ventricle. However in this case of double inversion, aorta carries saturated blood and pulmonary artery carries venous blood. So, normal physiological circulation is maintained. Our patient, a 38-years-old Bangladeshi male presented with palpitation, dizziness and effort intolerance (NYHAII) during exertion since childhood, which has recently become much worse. However, he had no history of central cyanosis, chest pain or syncope. We diagnosed him as a case of Corrected TGA and second-degree AV block with intermittent complete heart block. A Dual chamber permanent Pacemaker was inserted without any complications. No invasive treatment including corrective surgery was performed because patient’s cardiac function was almost normal. Patient became totally asymptomatic after pacemaker implantation Bangladesh Heart Journal 2022; 37(1): 77-80

Facile and Scalable Route to Access Rare Deoxy Amino Sugars for Nonulosonic Acid Aldolase Biosynthesis.

We presented a facile and scalable route for the synthesis of di-azido sugars via one-pot double inversion of the mono-benzoyl sugars by TBAN3 and studied the dependency pattern between solvent and protecting groups as well as the configuration of the neighboring and leaving groups. Moreover, we developed a chemical synthetic strategy for pseudaminic acid precursors (11 steps in 49%). Furthermore, we discussed the configuration of nonulosonic acid precursors for specificity of PseI and PmNanA enzymatic synthesis, permitting us to synthesize new nonulosonic acid derivatives for accessing Pse isomers.

PH-Regulated Single and Double Charge Inversions on PEI-Coated Surfaces.

The pH-regulated charge inversions on polyethylenimine (PEI)-coated surfaces are indispensable to their applications in biomaterials and nanomaterials. Various PEI-coated surfaces, where single charge inversion happens, have been extensively investigated, while the surfaces where double charge inversion appears are less reported. Here, using a molecular theory, we systematically study the pH-regulated charge density of PEI-coated surfaces. The results suggest whether single or double charge inversion happens depends on PEI affinity to the surface and the bare surface charge density. The region of double charge inversion is much smaller than that of single charge inversion, revealing the reason why double charge inversion is less observed in experiments. Besides, the charge inversions are significantly influenced by the solution condition. The present work provides a useful guideline to the selection of the coated materials and the parameters of PEI solution in the design of PEI-coated surfaces aiming to promote their applications in multifunctional nanomaterials.

Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis.

Background and ObjectivesMicroglia, the resident immune cell of the brain and retina, is widespread activated in the white and gray matter (GM) in multiple sclerosis (MS). The objective of this study is to evaluate the presence and number of hyperreflecting foci (HRF), considered clusters of activated and proliferating retinal microglia, and their association with clinical and radiologic disease parameters in relapsing-remitting MS (RRMS).MethodsAt baseline, 80 patients with RRMS underwent optical coherence tomography (OCT) and 3T-MRI (including 3-dimensional T1, fluid-attenuated inversion recovery, and double inversion recovery sequences), closed to their disease onset (6.3 ± 5.1 months). These patients were then clinically and radiologically followed up for a mean of 43 months, evaluating the no evidence of disease activity (NEDA) condition, further divided into clinical (cNEDA) and radiologic (rNEDA). Patients with a clinical history or MRI/OCT findings suggestive of optic neuritis (ON) were excluded from the study.ResultsCompared with healthy controls, the HRF number was significantly higher in the inner nuclear layer (INL) of patients with RRMS (19.55 ± 5.65 vs 13.84 ± 2.57, p < 0.001) and associated with INL volume (β: 1.21, p < 0.001). GM lesion volume significantly correlated with the INL HRF count (p = 0.008). Survival analysis revealed a significant association between INL HRF and both cNEDA (p = 0.017) and rNEDA (p = 0.002).DiscussionWe found a strong association between retinal microglial proliferation and cortical pathology in RRMS, a finding suggesting a possible underlying common immunopathologic mechanism. Furthermore, microglial activation at baseline was observed to predict subsequent inflammatory events, indicating that HRF might be a candidate prognostic biomarker worthy of further investigation.Classification of EvidenceThis study provides Class II evidence that in patients with early RRMS but without ON, the number of HRF on OCT of the retinal inner nuclear layer is associated with cNEDA and rNEDA.

A Novel Catalytic Route to Polymerizable Bicyclic Cyclic Carbonate Monomers from Carbon Dioxide.

A new catalytic route has been developed for the coupling of epoxides and CO2 affording polymerizable six‐membered bicyclic carbonates. Cyclic epoxides equipped with a β‐positioned OH group can be transformed into structurally diverse bicyclic cyclic carbonates in good yields and with high selectivity. Key to the chemo‐selectivity is the difference between the reactivity of syn‐ and anti‐configured epoxy alcohols, with the latter leading to six‐membered ring carbonate formation in the presence of a binary AlIII aminotriphenolate complex/DIPEA catalyst. X‐ray analyses show that the conversion of the syn‐configured substrate evolves via a standard double inversion pathway providing a five‐membered carbonate product, whereas the anti‐isomer allows for activation of the oxirane unit of the substrate opposite to the pendent alcohol. The potential use of these bicyclic products is shown in ring‐opening polymerization offering access to rigid polycarbonates with improved thermal resistance.

A Novel Catalytic Route to Polymerizable Bicyclic Cyclic Carbonate Monomers from Carbon Dioxide

AbstractA new catalytic route has been developed for the coupling of epoxides and CO2 affording polymerizable six‐membered bicyclic carbonates. Cyclic epoxides equipped with a β‐positioned OH group can be transformed into structurally diverse bicyclic cyclic carbonates in good yields and with high selectivity. Key to the chemo‐selectivity is the difference between the reactivity of syn‐ and anti‐configured epoxy alcohols, with the latter leading to six‐membered ring carbonate formation in the presence of a binary AlIII aminotriphenolate complex/DIPEA catalyst. X‐ray analyses show that the conversion of the syn‐configured substrate evolves via a standard double inversion pathway providing a five‐membered carbonate product, whereas the anti‐isomer allows for activation of the oxirane unit of the substrate opposite to the pendent alcohol. The potential use of these bicyclic products is shown in ring‐opening polymerization offering access to rigid polycarbonates with improved thermal resistance.

Determining the Effectiveness of Double Inversion Recovery (DIR) Brain MRI Sequence in Detecting Upper Spinal Cord Lesions in Multiple Sclerosis Patients (P1-1.Virtual)

Determining the Effectiveness of Double Inversion Recovery (DIR) Brain MRI Sequence in Detecting Upper Spinal Cord Lesions in Multiple Sclerosis Patients (P1-1.Virtual)

Fluid and White Matter Suppression: New Sensitive 3 T Magnetic Resonance Imaging Contrasts for Cortical Lesion Detection in Multiple Sclerosis.

Cortical lesions are common in multiple sclerosis (MS), but their visualization is challenging on conventional magnetic resonance imaging. The uniform image derived from magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE uni ) detects cortical lesions with a similar rate as the criterion standard sequence, double inversion recovery. Fluid and white matter suppression (FLAWS) provides multiple reconstructed contrasts acquired during a single acquisition. These contrasts include FLAWS minimum image (FLAWS min ), which provides an exquisite sensitivity to the gray matter signal and therefore may facilitate cortical lesion identification, as well as high contrast FLAWS (FLAWS hco ), which gives a contrast that is similar to one of MP2RAGE uni . In this study, we compared the manual detection rate of cortical lesions on MP2RAGE uni , FLAWS min , and FLAWS hco in MS patients. Furthermore, we assessed whether the combined detection rate on FLAWS min and FLAWS hco was superior to MP2RAGE uni for cortical lesions identification. Last, we compared quantitative T1 maps (qT1) provided by both MP2RAGE and FLAWS in MS lesions. We included 30 relapsing-remitting MS patients who underwent MP2RAGE and FLAWS magnetic resonance imaging with isotropic spatial resolution of 1 mm at 3 T. Cortical lesions were manually segmented by consensus of 3 trained raters and classified as intracortical or leukocortical lesions on (1) MP2RAGE uniform/flat images, (2) FLAWS min , and (3) FLAWS hco . In addition, segmented lesions on FLAWS min and FLAWS hco were merged to produce a union lesion map (FLAWS min + hco ). Number and volume of all cortical, intracortical, and leukocortical lesions were compared among MP2RAGE uni , FLAWS min , and FLAWS hco using Friedman test and between MP2RAGE uni and FLAWS min + hco using Wilcoxon signed rank test. The FLAWS T1 maps were then compared with the reference MP2RAGE T1 maps using relative differences in percentage. In an exploratory analysis, individual cortical lesion counts of the 3 raters were compared, and interrater variability was quantified using Fleiss ϰ. In total, 633 segmentations were made on the 3 contrasts, corresponding to 355 cortical lesions. The median number and volume of single cortical, intracortical, and leukocortical lesions were comparable among MP2RAGE uni , FLAWS min , and FLAWS hco . In patients with cortical lesions (22/30), median cumulative lesion volume was larger on FLAWS min (587 μL; IQR, 1405 μL) than on MP2RAGE uni (490 μL; IQR, 990 μL; P = 0.04), whereas there was no difference between FLAWS min and FLAWS hco , or FLAWS hco and MP2RAGE uni . FLAWS min + hco showed significantly greater numbers of cortical (median, 4.5; IQR, 15) and leukocortical (median, 3.5; IQR, 12) lesions than MP2RAGE uni (median, 3; IQR, 10; median, 2.5; IQR, 7; both P < 0.001). Interrater agreement was moderate on MP2RAGE uni (ϰ = 0.582) and FLAWS hco (ϰ = 0.584), but substantial on FLAWS min (ϰ = 0.614). qT1 in lesions was similar between MP2RAGE and FLAWS. Cortical lesions identification in FLAWS min and FLAWS hco was comparable to MP2RAGE uni . The combination of FLAWS min and FLAWS hco allowed to identify a higher number of cortical lesions than MP2RAGE uni , whereas qT1 maps did not differ between the 2 acquisition schemes.

Epistatic selection on a selfish Segregation Distorter supergene - drive, recombination, and genetic load.

Meiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation resulting in preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing one of a pair of alternative alleles. While at least two loci are important for male drive-the driver and the target-linked modifiers can enhance drive, creating selection pressure to suppress recombination. In this work, we investigate the evolution and genomic consequences of an autosomal, multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversions on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over, and with wildtype chromosomes via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world and have implications for supergene evolution broadly.

Uncertainty-Aware and Lesion-Specific Image Synthesis in Multiple Sclerosis Magnetic Resonance Imaging: A Multicentric Validation Study.

Generative adversarial networks (GANs) can synthesize high-contrast MRI from lower-contrast input. Targeted translation of parenchymal lesions in multiple sclerosis (MS), as well as visualization of model confidence further augment their utility, provided that the GAN generalizes reliably across different scanners. We here investigate the generalizability of a refined GAN for synthesizing high-contrast double inversion recovery (DIR) images and propose the use of uncertainty maps to further enhance its clinical utility and trustworthiness. A GAN was trained to synthesize DIR from input fluid-attenuated inversion recovery (FLAIR) and T1w of 50 MS patients (training data). In another 50 patients (test data), two blinded readers (R1 and R2) independently quantified lesions in synthetic DIR (synthDIR), acquired DIR (trueDIR) and FLAIR. Of the 50 test patients, 20 were acquired on the same scanner as training data (internal data), while 30 were scanned at different scanners with heterogeneous field strengths and protocols (external data). Lesion-to-Background ratios (LBR) for MS-lesions vs. normal appearing white matter, as well as image quality parameters were calculated. Uncertainty maps were generated to visualize model confidence. Significantly more MS-specific lesions were found in synthDIR compared to FLAIR (R1: 26.7 ± 2.6 vs. 22.5 ± 2.2 p < 0.0001; R2: 22.8 ± 2.2 vs. 19.9 ± 2.0, p = 0.0005). While trueDIR remained superior to synthDIR in R1 [28.6 ± 2.9 vs. 26.7 ± 2.6 (p = 0.0021)], both sequences showed comparable lesion conspicuity in R2 [23.3 ± 2.4 vs. 22.8 ± 2.2 (p = 0.98)]. Importantly, improvements in lesion counts were similar in internal and external data. Measurements of LBR confirmed that lesion-focused GAN training significantly improved lesion conspicuity. The use of uncertainty maps furthermore helped discriminate between MS lesions and artifacts. In conclusion, this multicentric study confirms the external validity of a lesion-focused Deep-Learning tool aimed at MS imaging. When implemented, uncertainty maps are promising to increase the trustworthiness of synthetic MRI.

Carbazole Isomerism in Helical Radical Cations: Spin Delocalization and SOMO-HOMO Level Inversion in the Diradical State.

We report a new molecular design to afford persistent chiral organic open-shell systems with configurational stability and an inversion in energy of the singly occupied molecular orbital (SOMO) and the highest doubly occupied molecular orbital (HOMO) for both mono- and diradical states. The unpaired electron delocalization within the designed extended helical π-conjugated systems is a crucial factor to reach chemical stabilities, which is not obtained using the classical steric protection approach. The unique features of the obtained helical monoradicals allow an exploration of the chiral intramolecular electron transfer (IET) process in solvents of different polarity by means of optical and chiroptical spectroscopies, resulting in an unprecedented electronic circular dichroism (ECD) sign inversion for the radical transitions. We also characterized the corresponding helical diradicals, which show near-infrared electronic circular dichroism at wavelengths up to 1100 nm and an antiferromagnetic coupling between the spins, with an estimated singlet-triplet gap (ΔEST) of about -1.2 kcal mol-1. The study also revealed an intriguing double SOMO-HOMO inversion (SHI) electronic configuration for these diradicals, providing new insight regarding the peculiar energetic ordering of radical orbitals and the impact on the corresponding (chiral) optoelectronic properties.