Validation of echo planar imaging based diffusion-weighted magnetic resonance imaging on a 0.35 T MR-Linac.

Background and Purpose: The feasibility of acquiring diffusion-weighted imaging (DWI) images on an MR-Linac for quantitative response assessment during radiotherapy was explored. DWI data obtained with a Spin Echo Echo Planar Imaging sequence adapted for a 0.35 T MR-Linac were examined and compared with DWI data from a conventional 3 T scanner. Materials and Methods: Apparent diffusion coefficient (ADC) measurements and a distortion correction technique were investigated using DWI-calibrated phantoms and in the brains of seven volunteers. All DWI utilized two phase-encoding directions for distortion correction and off-resonance field estimation. ADC maps in the brain were analyzed for automatically segmented normal tissues. Results: Phantom ADC measurements on the MR-Linac were within a 3 % margin of those recorded by the 3 T scanner. The maximum distortion observed in the phantom was 2.0 mm prior to correction and 1.1 mm post-correction on the MR-Linac, compared to 6.0 mm before correction and 3.6 mm after correction at 3 T. In vivo, the average ADC values for gray and white matter exhibited variations of 14 % and 4 %, respectively, for different selections of b-values on the MR-Linac. Distortions in brain images before correction, estimated through the off-resonance field, reached 2.7 mm on the MR-Linac and 12 mm at 3 T. Conclusion: Accurate ADC measurements are achievable on a 0.35 T MR-Linac, both in phantom and in vivo. The selection of b-values significantly influences ADC values in vivo. DWI on the MR-Linac demonstrated lower distortion levels, with a maximum distortion reduced to 1.1 mm after correction.

Generalizable attention U-Net for segmentation of fibroglandular tissue and background parenchymal enhancement in breast DCE-MRI.

OBJECTIVES: Development of automated segmentation models enabling standardized volumetric quantification of fibroglandular tissue (FGT) from native volumes and background parenchymal enhancement (BPE) from subtraction volumes of dynamic contrast-enhanced breast MRI. Subsequent assessment of the developed models in the context of FGT and BPE Breast Imaging Reporting and Data System (BI-RADS)-compliant classification. METHODS: For the training and validation of attention U-Net models, data coming from a single 3.0-T scanner was used. For testing, additional data from 1.5-T scanner and data acquired in a different institution with a 3.0-T scanner was utilized. The developed models were used to quantify the amount of FGT and BPE in 80 DCE-MRI examinations, and a correlation between these volumetric measures and the classes assigned by radiologists was performed. RESULTS: To assess the model performance using application-relevant metrics, the correlation between the volumes of breast, FGT, and BPE calculated from ground truth masks and predicted masks was checked. Pearson correlation coefficients ranging from 0.963 ± 0.004 to 0.999 ± 0.001 were achieved. The Spearman correlation coefficient for the quantitative and qualitative assessment, i.e., classification by radiologist, of FGT amounted to 0.70 (p < 0.0001), whereas BPE amounted to 0.37 (p = 0.0006). CONCLUSIONS: Generalizable algorithms for FGT and BPE segmentation were developed and tested. Our results suggest that when assessing FGT, it is sufficient to use volumetric measures alone. However, for the evaluation of BPE, additional models considering voxels' intensity distribution and morphology are required. CRITICAL RELEVANCE STATEMENT: A standardized assessment of FGT density can rely on volumetric measures, whereas in the case of BPE, the volumetric measures constitute, along with voxels' intensity distribution and morphology, an important factor. KEY POINTS: • Our work contributes to the standardization of FGT and BPE assessment. • Attention U-Net can reliably segment intricately shaped FGT and BPE structures. • The developed models were robust to domain shift.

Systematic analysis of changes in radiomics features during dynamic breast-MRI: Evaluation of specific biomarkers.

OBJECTIVES: In this retrospective, single-center study we investigate the changes of radiomics features during dynamic breast-MRI for healthy tissue compared to benign and malignant lesions. METHODS: 60 patients underwent breast-MRI using a dynamic 3D gradient-echo sequence. Changes of 34 texture features (TF) in 30 benign and 30 malignant lesions were calculated for 5 dynamic datasets and corresponding 4 subtraction datasets. Statistical analysis was performed with ANOVA, and systematic changes in features were described by linear and polynomial regression models. RESULTS: ANOVA revealed significant differences (p < 0.05) between normal tissue and lesions in 13 TF, compared to 9 TF between benign and malignant lesions. Most TF showed significant differences in early dynamic and subtraction datasets. TF associated with homogeneity were suitable to discriminate between healthy parenchyma and lesions, whereas run-length features were more suitable to discriminate between benign and malignant lesions. Run length nonuniformity (RLN) was the only feature able to distinguish between all three classes with an AUC of 88.3%. Characteristic changes were observed with a systematic increase or decrease for most TF with mostly polynomial behavior. Slopes showed earlier peaks in malignant lesions, compared to benign lesions. Mean values for the coefficient of determination were higher during subtraction sequences, compared to dynamic sequences (benign: 0.98 vs 0. 72; malignant: 0.94 vs 0.74). CONCLUSIONS: TF of breast lesions follow characteristic patterns during dynamic breast-MRI, distinguishing benign from malignant lesions. Early dynamic and subtraction datasets are particularly suitable for texture analysis in breast-MRI. Features associated with tissue homogeneity seem to be indicative of benign lesions.

Induced Fit and Mobility of Cycloalkanes within Nanometer-Sized Confinements at 5 K.

Host-guest architectures provide ideal systems for investigating site-specific physical and chemical effects. Condensation events in nanometer-sized confinements are particularly interesting for the investigation of intermolecular and molecule-surface interactions. They may be accompanied by conformational adjustments representing induced fit packing patterns. Here, we report that the symmetry of small clusters formed upon condensation, their registry with the substrate, their lateral packing, and their adsorption height are characteristically modified by the packing of cycloalkanes in confinements. While cyclopentane and cycloheptane display cooperativity upon filling of the hosting pores, cyclooctane and to a lesser degree cyclohexane diffusively redistribute to more favored adsorption sites. The dynamic behavior of cyclooctane is surprising at 5 K given the cycloalkane melting point of >0 °C. The site-specific modification of the interaction and behavior of adsorbates in confinements plays a crucial role in many applications of three-dimensional porous materials as gas storage agents or catalysts/biocatalysts.

Watching nanostructure growth: kinetically controlled diffusion and condensation of Xe in a surface metal organic network.

Diffusion, nucleation and growth provide the fundamental access to control nanostructure growth. In this study, the temperature activated diffusion of Xe at and between different compartments of an on-surface metal organic coordination network on Cu(111) has been visualized in real space. Xe atoms adsorbed at lower energy sites become mobile with increased temperature and gradually populate energetically more favourable binding sites or remain in a delocalized 'fluid' form confined to diffusion along a topological subset of the on-surface network. These diffusion pathways can be studied individually under kinetic control via the chosen thermal energy kT of the sample and are determined by the network and sample architecture. The spatial distribution of Xe in its different modes of mobility and the time scales of the motion is revealed by Scanning Tunneling Microscopy (STM) at variable temperatures up to 40 K and subsequent cooling to 4 K. The system provides insight into the diffusion of a van der Waals gas on a complex structured surface and its nucleation and coarsening/growth into larger condensates at elevated temperature under thermodynamic conditions.

Phase Transitions in Confinements: Controlling Solid to Fluid Transitions of Xenon Atoms in an On-Surface Network.

This study reports on "phase" transitions of Xe condensates in on-surface confinements induced by temperature changes and local probe excitation. The pores of a metal-organic network occupied with 1 up to 9 Xe atoms are investigated in their propensity to undergo "condensed solid" to "confined fluid" transitions. Different transition temperatures are identified, which depend on the number of Xe atoms in the condensate and relate to the stability of the Xe clustering in the condensed "phase." This work reveals the feature-rich behavior of transitions of confined planar condensates, which provide a showcase toward future "phase-transition" storage media patterned by self-assembly. This work is also of fundamental interest as it paves the way to real space investigations of reversible solid to fluid transitions of magic cluster condensates in an array of extremely well-defined quantum confinements.

The Different Faces of 4'-Pyrimidinyl-Functionalized 4,2':6',4''-Terpyridines: Metal-Organic Assemblies from Solution and on Au(111) and Cu(111) Surface Platforms.

A comparative investigation of crystal growth from solution and on-surface assembly in vacuo between copper and three 4'-(2-R-pyrimidin-5-yl)-4,2':6',4''-terpyridines, with R = H (1), Me (2), or Et (3), is presented. In solution, ligand 3 combines with copper(II) acetate or copper(I) triflate in MeOH solution to give [Cu2(OAc)4(3)]n or {[Cu(3)(OMe)(MeOH)][CF3SO3]·MeOH}n. In [Cu2(OAc)4(3)]n, paddle-wheel {Cu2(µ-OAc)4} nodes direct the assembly of one-dimensional (1D) zigzag chains which pack into two-dimensional (2D) sheets. In {[Cu(3)(OMe)(MeOH)][CF3SO3]·MeOH}n, the solvent is a ligand and also generates {Cu2(µ-OMe)2} units which function as planar 4-connecting nodes to generate a 2D (4,4) net with ligand 3. On Au(111) or Cu(111) surfaces in vacuo, no additional solvent or anions are involved in the assembly. The different substituents in 1, 2, or 3 allow precise molecular resolution imaging in scanning tunneling microscopy. On Au(111), 1 and 2 assemble into close-packed assemblies, while 3 forms a regular porous network. The deposition of Cu adatoms results in reorganization leading to ladder-shaped surface metal-organic motifs. These on-surface coordination assemblies are independent of the 4'-substituent in the 4,2':6',4''-tpy and are reproduced on Cu(111) where Cu adatoms are available during the deposition and relaxation process at room temperature. Upon annealing at elevated temperatures, the original surface assemblies of 1 and 3 are modified and a transition from ladders into rhomboid structures is observed; for 2, a further quasi-hexagonal nanoporous network is observed.

Adsorbate-Induced Modification of the Confining Barriers in a Quantum Box Array.

Quantum devices depend on addressable elements, which can be modified separately and in their mutual interaction. Self-assembly at surfaces, for example, formation of a porous (metal-) organic network, provides an ideal way to manufacture arrays of identical quantum boxes, arising in this case from the confinement of the electronic (Shockley) surface state within the pores. We show that the electronic quantum box state as well as the interbox coupling can be modified locally to a varying extent by a selective choice of adsorbates, here C60, interacting with the barrier. In view of the wealth of differently acting adsorbates, this approach allows for engineering quantum states in on-surface network architectures.

Long-range ferrimagnetic order in a two-dimensional supramolecular Kondo lattice.

Realization of long-range magnetic order in surface-supported two-dimensional systems has been challenging, mainly due to the competition between fundamental magnetic interactions as the short-range Kondo effect and spin-stabilizing magnetic exchange interactions. Spin-bearing molecules on conducting substrates represent a rich platform to investigate the interplay of these fundamental magnetic interactions. Here we demonstrate the direct observation of long-range ferrimagnetic order emerging in a two-dimensional supramolecular Kondo lattice. The lattice consists of paramagnetic hexadeca-fluorinated iron phthalocyanine (FeFPc) and manganese phthalocyanine (MnPc) molecules co-assembled into a checkerboard pattern on single-crystalline Au(111) substrates. Remarkably, the remanent magnetic moments are oriented in the out-of-plane direction with significant contribution from orbital moments. First-principles calculations reveal that the FeFPc-MnPc antiferromagnetic nearest-neighbour coupling is mediated by the Ruderman-Kittel-Kasuya-Yosida exchange interaction via the Au substrate electronic states. Our findings suggest the use of molecular frameworks to engineer novel low-dimensional magnetically ordered materials and their application in molecular quantum devices.

Molecular Chessboard Assemblies Sorted by Site-Specific Interactions of Out-of-Plane d-Orbitals with a Semimetal Template.

We show that highly ordered two-dimensional (2D) chessboard arrays consisting of a periodic arrangement of two different molecules can be obtained by self-assembly of unsubstituted metal-phthalocyanines (metal-Pcs) on a suitable substrate serving as the template. Specifically, CuPc + MnPc and CuPc + CoPc mixtures sort into highly ordered Cu/Mn and Cu/Co chessboard arrays on the square p(10 × 10) reconstruction of bismuth on Cu(100). Such created bimolecular chessboard assemblies emerge from the site-specific interactions between the central transition-metal ions and the periodically reconstructed substrate. This work provides a conceptually new approach to induce 2D chessboard patterns in that no functionalization of the molecules is needed.

Configuring Electronic States in an Atomically Precise Array of Quantum Boxes.

A 2D array of electronically coupled quantum boxes is fabricated by means of on-surface self-assembly assuring ultimate precision of each box. The quantum states embedded in the boxes are configured by adsorbates, whose occupancy is controlled with atomic precision. The electronic interbox coupling can be maintained or significantly reduced by proper arrangement of empty and filled boxes.

Van der Waals interactions and the limits of isolated atom models at interfaces.

Van der Waals forces are among the weakest, yet most decisive interactions governing condensation and aggregation processes and the phase behaviour of atomic and molecular matter. Understanding the resulting structural motifs and patterns has become increasingly important in studies of the nanoscale regime. Here we measure the paradigmatic van der Waals interactions represented by the noble gas atom pairs Ar-Xe, Kr-Xe and Xe-Xe with a Xe-functionalized tip of an atomic force microscope at low temperature. Individual rare gas atoms were fixed at node sites of a surface-confined two-dimensional metal-organic framework. We found that the magnitude of the measured force increased with the atomic radius, yet detailed simulation by density functional theory revealed that the adsorption induced charge redistribution strengthened the van der Waals forces by a factor of up to two, thus demonstrating the limits of a purely atomic description of the interaction in these representative systems.

Programmed assembly of 4,2':6',4''-terpyridine derivatives into porous, on-surface networks.

The use of divergent, V-shaped, 4,2':6',4''-terpyridine building blocks that self-assemble into hydrogen-bonded domains and upon addition of copper atoms undergo metallation with concomitant transformation into a coordination network is described; multiple energetically similar structural motifs are observed in both hydrogen-bonded and adatom-coordinated networks.

Interplay of weak interactions in the atom-by-atom condensation of xenon within quantum boxes.

Condensation processes are of key importance in nature and play a fundamental role in chemistry and physics. Owing to size effects at the nanoscale, it is conceptually desired to experimentally probe the dependence of condensate structure on the number of constituents one by one. Here we present an approach to study a condensation process atom-by-atom with the scanning tunnelling microscope, which provides a direct real-space access with atomic precision to the aggregates formed in atomically defined 'quantum boxes'. Our analysis reveals the subtle interplay of competing directional and nondirectional interactions in the emergence of structure and provides unprecedented input for the structural comparison with quantum mechanical models. This approach focuses on-but is not limited to-the model case of xenon condensation and goes significantly beyond the well-established statistical size analysis of clusters in atomic or molecular beams by mass spectrometry.

Probing the spatial and momentum distribution of confined surface states in a metal coordination network.

The Shockley surface state on Cu(111) reacts sensitively to the perturbation by molecular adsorbates on the surface. In the porous structure of a metal-coordinated molecular network on Cu(111), the surface state is confined to a series of discrete states. Energy and momentum of eigenstates in the pores are related to both the energy dispersion of the free surface state and the geometric and energetic details of the confining barrier formed by the molecular network. The penetration of the confined state into the barrier is found to be sensitive to the constituting architectural elements.

Controlling the dimensionality of on-surface coordination polymers via endo- or exoligation.

The formation of on-surface coordination polymers is controlled by the interplay of chemical reactivity and structure of the building blocks, as well as by the orientating role of the substrate registry. Beyond the predetermined patterns of structural assembly, the chemical reactivity of the reactants involved may provide alternative pathways in their aggregation. Organic molecules, which are transformed in a surface reaction, may be subsequently trapped via coordination of homo- or heterometal adatoms, which may also play a role in the molecular transformation. The amino-functionalized perylene derivative, 4,9-diaminoperylene quinone-3,10-diimine (DPDI), undergoes specific levels of dehydrogenation (-1 H2 or -3 H2) depending on the nature of the present adatoms (Fe, Co, Ni or Cu). In this way, the molecule is converted to an endo- or an exoligand, possessing a concave or convex arrangement of ligating atoms, which is decisive for the formation of either 1D or 2D coordination polymers.

Chirality transfer in 1D self-assemblies: influence of H-bonding vs metal coordination between dicyano[7]helicene enantiomers.

Chiral recognition as well as chirality transfer in supramolecular self-assembly and on-surface coordination is studied for the enantiopure 6,13-dicyano[7]helicene building block. It is remarkable that, with this helical molecule, both H-bonded chains and metal-coordinated chains can be formed on the same substrate, thereby allowing for a direct comparison of the chain bonding motifs and their effects on the self-assembly in experiment and theory. Conformational flexure and both adsorbate/adsorbent and intermolecular interactions can be identified as factors influencing the chiral recognition at the binding site. The observed H-bonded chains are chiral, however, the overall appearance of Cu-coordinated chains is no longer chiral. The study was performed via scanning tunneling microscopy, X-ray-photoelectron spectroscopy and density functional theory calculations. We show a significant influence of the molecular flexibility and the type of bonding motif on the chirality transfer in the 1D self-assembly.