3D Bioprinting and Near-Field Electrospinning Composite Scaffolds for the Bone-Ligament Interface

3D bioprinting is an additive manufacturing technique that can utilize a range of bioactive materials to construct specific architectures that mimic native tissue. Near-field electrospinning (NFE) offers precise alignment control to create non-woven mats with high tensile strengths. We built a custom E-spin printer that enables layer-by-layer alternating deposition between 3D bioprinting and NFE to create composite scaffolds for the bone-ligament interface. This complex region is difficult to simulate due to its functionally graded mechanical and biochemical properties. We created NFE poly(caprolactone) highly aligned micro-fibers which formed collagen fibril-like bundles. Poly(ethylene glycol) diacrylate with decellularized bone was encased in the PCL fibers to create bony ligament support structures in a composite scaffold. Cytotoxicity of all materials was determined through a Live/Dead assay (Thermo Fisher) with NIH/3T3 cells. The materials and the composite scaffold were seeded with 3T3 cells and cultured for three days before undergoing an immunocytochemistry staining (ICC) to assess cell adhesion and spreading. Increased adhesion and spreading on decellularized bone scaffolds along with cell elongation in the direction of the fibers suggests the ability of the scaffold to encourage osteoblastic differentiation and ligamentous tissue formation, though a longitudinal study is still underway. Mechanical results suggest that the composite scaffolds have increased compressive strength over PEGDA alone as the PCL fibers constrict horizontal elongation, thus yielding a higher compressive modulus. The PCL fibers demonstrated a tensile strength approaching native ligament (3.96 ± 1.10 MPa), which shows promise as the ligament phase of the scaffold. The E-spin printer’s versatility with materials of disparate viscosities enabled the layer-by-layer fabrication of composite (PCL/PEGDA+bone) scaffolds that begin to mimic the complex nature of the bone-ligament interface

Improvements in Between-Vendor MRI Harmonization of Renal T2 Mapping using Stimulated Echo Compensation

BACKGROUND: T2 mapping is valuable to evaluate pathophysiology in kidney disease. However, variations in T2 relaxation time measurements across MR scanners and vendors may occur requiring additional correction. PURPOSE: To harmonize renal T2 measurements between MR vendor platforms, and use an extended-phase-graph-based fitting method ("StimFit") to correct stimulated echoes and reduce between-vendor variations. STUDY TYPE: Prospective. SUBJECTS: 8 healthy "travelling" volunteers (37.5% female, 32 ± 6 years) imaged on four MRI systems across three vendors at four sites, 10 healthy volunteers (50% female, 32 ± 8 years) scanned multiple times on a given MR scanner for repeatability evaluation. ISMRM/NIST system phantom scanned for evaluation of T2 accuracy. FIELD STRENGTH/SEQUENCE: 3T, multiecho spin-echo sequence. ASSESSMENT: T2 images fit using conventional monoexponential fitting and "StimFit." Mean absolute percentage error (MAPE) of phantom measurements with reference T2 values. Average cortex and medulla T2 values compared between MR vendors, with masks obtained from T2 -weighted images and T1 maps. Full-width-at-half-maximum (FWHM) T2 distributions to evaluate local homogeneity of measurements. STATISTICAL TESTS: Coefficient of variation (CV), linear mixed-effects model, analysis of variance, student's t-tests, Bland-Altman plots, P-value <0.05 considered statistically significant. RESULTS: In the ISMRM/NIST phantom, "StimFit" reduced the MAPE from 4.9%, 9.1%, 24.4%, and 18.1% for the four sites (three vendors) to 3.3%, 3.0%, 6.6%, and 4.1%, respectively. In vivo, there was a significant difference in kidney T2 measurements between vendors using a monoexponential fit, but not with "StimFit" (P = 0.86 and 0.92, cortex and medulla, respectively). The intervendor CVs of T2 measures were reduced from 8.0% to 2.6% (cortex) and 7.1% to 2.8% (medulla) with StimFit, resulting in no significant differences for the CVs of intravendor repeat acquisitions (P = 0.13 and 0.05). "StimFit" significantly reduced the FWHM of T2 distributions in the cortex and whole kidney. DATA CONCLUSION: Stimulated-echo correction reduces renal T2 variation across MR vendor platforms. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1

Mapping the functional brain state of a world champion freediver in static dry apnea

peer reviewedVoluntary apnea showcases extreme human adaptability in trained individuals like professional free divers. We evaluated the psychological and physiological adaptation and the functional cerebral changes using electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI) to 6.5 min of dry static apnea performed by a world champion free diver. Compared to resting state at baseline, breath holding was characterized by increased EEG power and functional connectivity in the alpha band, along with decreased delta band connectivity. fMRI connectivity was increased within the default mode network (DMN) and visual areas but decreased in pre- and postcentral cortices. While these changes occurred in regions overlapping with cerebral signatures of several meditation practices, they also display some unique features that suggest an altered somatosensory integration. As suggested by self-reports, these findings could reflect the ability of elite free divers to create a state of sensory dissociation when performing prolonged apnea

Technical recommendations for clinical translation of renal MRI: a consensus project of the Cooperation in Science and Technology Action PARENCHIMA.

PURPOSE: The potential of renal MRI biomarkers has been increasingly recognised, but clinical translation requires more standardisation. The PARENCHIMA consensus project aims to develop and apply a process for generating technical recommendations on renal MRI. METHODS: A task force was formed in July 2018 focused on five methods. A draft process for attaining consensus was distributed publicly for consultation and finalised at an open meeting (Prague, October 2018). Four expert panels completed surveys between October 2018 and March 2019, discussed results and refined the surveys at a face-to-face meeting (Aarhus, March 2019) and completed a second round (May 2019). RESULTS: A seven-stage process was defined: (1) formation of expert panels; (2) definition of the context of use; (3) literature review; (4) collection and comparison of MRI protocols; (5) consensus generation by an approximate Delphi method; (6) reporting of results in vendor-neutral and vendor-specific terms; (7) ongoing review and updating. Application of the process resulted in 166 consensus statements. CONCLUSION: The process generated meaningful technical recommendations across very different MRI methods, while allowing for improvement and refinement as open issues are resolved. The results are likely to be widely supported by the renal MRI community and thereby promote more harmonisation

Consensus-based technical recommendations for clinical translation of renal ASL MRI

Objectives: To develop technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5T and 3T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-center clinical studies.Methods: An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting.Results: Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labeling with a single-slice spin-echo EPI readout with background suppression, and a simple but robust quantification model.Discussion: This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data becomes available, since the renal ASL literature is rapidly expanding

Technical recommendations for clinical translation of renal MRI: a consensus project of the Cooperation in Science and Technology Action PARENCHIMA

Purpose The potential of renal MRI biomarkers has been increasingly recognised, but clinical translation requires more standardisation. The PARENCHIMA consensus project aims to develop and apply a process for generating technical recommendations on renal MRI. Methods A task force was formed in July 2018 focused on fve methods. A draft process for attaining consensus was distributed publicly for consultation and fnalised at an open meeting (Prague, October 2018). Four expert panels completed surveys between October 2018 and March 2019, discussed results and refned the surveys at a face-to-face meeting (Aarhus, March 2019) and completed a second round (May 2019). Results A seven-stage process was defned: (1) formation of expert panels; (2) defnition of the context of use; (3) literature review; (4) collection and comparison of MRI protocols; (5) consensus generation by an approximate Delphi method; (6) reporting of results in vendor-neutral and vendor-specifc terms; (7) ongoing review and updating. Application of the process resulted in 166 consensus statements. Conclusion The process generated meaningful technical recommendations across very diferent MRI methods, while allowing for improvement and refnement as open issues are resolved. The results are likely to be widely supported by the renal MRI community and thereby promote more harmonisation

Correction to: Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

The article Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI

Correction to: Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

The article Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI

Comparative cellular analysis of motor cortex in human, marmoset and mouse

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations