Zero-DeepSub: Zero-shot deep subspace reconstruction for rapid multiparametric quantitative MRI using 3D-QALAS.

PURPOSE: To develop and evaluate methods for (1) reconstructing 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) time-series images using a low-rank subspace method, which enables accurate and rapid T1 and T2 mapping, and (2) improving the fidelity of subspace QALAS by combining scan-specific deep-learning-based reconstruction and subspace modeling. THEORY AND METHODS: A low-rank subspace method for 3D-QALAS (i.e., subspace QALAS) and zero-shot deep-learning subspace method (i.e., Zero-DeepSub) were proposed for rapid and high fidelity T1 and T2 mapping and time-resolved imaging using 3D-QALAS. Using an ISMRM/NIST system phantom, the accuracy and reproducibility of the T1 and T2 maps estimated using the proposed methods were evaluated by comparing them with reference techniques. The reconstruction performance of the proposed subspace QALAS using Zero-DeepSub was evaluated in vivo and compared with conventional QALAS at high reduction factors of up to nine-fold. RESULTS: Phantom experiments showed that subspace QALAS had good linearity with respect to the reference methods while reducing biases and improving precision compared to conventional QALAS, especially for T2 maps. Moreover, in vivo results demonstrated that subspace QALAS had better g-factor maps and could reduce voxel blurring, noise, and artifacts compared to conventional QALAS and showed robust performance at up to nine-fold acceleration with Zero-DeepSub, which enabled whole-brain T1, T2, and PD mapping at 1 mm isotropic resolution within 2 min of scan time. CONCLUSION: The proposed subspace QALAS along with Zero-DeepSub enabled high fidelity and rapid whole-brain multiparametric quantification and time-resolved imaging.

SSL-QALAS: Self-Supervised Learning for rapid multiparameter estimation in quantitative MRI using 3D-QALAS.

PURPOSE: To develop and evaluate a method for rapid estimation of multiparametric T1 , T2 , proton density, and inversion efficiency maps from 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) measurements using self-supervised learning (SSL) without the need for an external dictionary. METHODS: An SSL-based QALAS mapping method (SSL-QALAS) was developed for rapid and dictionary-free estimation of multiparametric maps from 3D-QALAS measurements. The accuracy of the reconstructed quantitative maps using dictionary matching and SSL-QALAS was evaluated by comparing the estimated T1 and T2 values with those obtained from the reference methods on an International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom. The SSL-QALAS and the dictionary-matching methods were also compared in vivo, and generalizability was evaluated by comparing the scan-specific, pre-trained, and transfer learning models. RESULTS: Phantom experiments showed that both the dictionary-matching and SSL-QALAS methods produced T1 and T2 estimates that had a strong linear agreement with the reference values in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom. Further, SSL-QALAS showed similar performance with dictionary matching in reconstructing the T1 , T2 , proton density, and inversion efficiency maps on in vivo data. Rapid reconstruction of multiparametric maps was enabled by inferring the data using a pre-trained SSL-QALAS model within 10 s. Fast scan-specific tuning was also demonstrated by fine-tuning the pre-trained model with the target subject's data within 15 min. CONCLUSION: The proposed SSL-QALAS method enabled rapid reconstruction of multiparametric maps from 3D-QALAS measurements without an external dictionary or labeled ground-truth training data.

3D-EPI blip-up/down acquisition (BUDA) with CAIPI and joint Hankel structured low-rank reconstruction for rapid distortion-free high-resolution T 2 * mapping.

PURPOSE: This work aims to develop a novel distortion-free 3D-EPI acquisition and image reconstruction technique for fast and robust, high-resolution, whole-brain imaging as well as quantitative T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping. METHODS: 3D Blip-up and -down acquisition (3D-BUDA) sequence is designed for both single- and multi-echo 3D gradient recalled echo (GRE)-EPI imaging using multiple shots with blip-up and -down readouts to encode B0 field map information. Complementary k-space coverage is achieved using controlled aliasing in parallel imaging (CAIPI) sampling across the shots. For image reconstruction, an iterative hard-thresholding algorithm is employed to minimize the cost function that combines field map information informed parallel imaging with the structured low-rank constraint for multi-shot 3D-BUDA data. Extending 3D-BUDA to multi-echo imaging permits T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping. For this, we propose constructing a joint Hankel matrix along both echo and shot dimensions to improve the reconstruction. RESULTS: Experimental results on in vivo multi-echo data demonstrate that, by performing joint reconstruction along with both echo and shot dimensions, reconstruction accuracy is improved compared to standard 3D-BUDA reconstruction. CAIPI sampling is further shown to enhance image quality. For T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping, parameter values from 3D-Joint-CAIPI-BUDA and reference multi-echo GRE are within limits of agreement as quantified by Bland-Altman analysis. CONCLUSIONS: The proposed technique enables rapid 3D distortion-free high-resolution imaging and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping. Specifically, 3D-BUDA enables 1-mm isotropic whole-brain imaging in 22 s at 3T and 9 s on a 7T scanner. The combination of multi-echo 3D-BUDA with CAIPI acquisition and joint reconstruction enables distortion-free whole-brain T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping in 47 s at 1.1 × 1.1 × 1.0 mm3 resolution.

Scan-specific artifact reduction in k-space (SPARK) neural networks synergize with physics-based reconstruction to accelerate MRI.

PURPOSE: To develop a scan-specific model that estimates and corrects k-space errors made when reconstructing accelerated MRI data. METHODS: Scan-specific artifact reduction in k-space (SPARK) trains a convolutional-neural-network to estimate and correct k-space errors made by an input reconstruction technique by back-propagating from the mean-squared-error loss between an auto-calibration signal (ACS) and the input technique's reconstructed ACS. First, SPARK is applied to generalized autocalibrating partially parallel acquisitions (GRAPPA) and demonstrates improved robustness over other scan-specific models, such as robust artificial-neural-networks for k-space interpolation (RAKI) and residual-RAKI. Subsequent experiments demonstrate that SPARK synergizes with residual-RAKI to improve reconstruction performance. SPARK also improves reconstruction quality when applied to advanced acquisition and reconstruction techniques like 2D virtual coil (VC-) GRAPPA, 2D LORAKS, 3D GRAPPA without an integrated ACS region, and 2D/3D wave-encoded imaging. RESULTS: SPARK yields SSIM improvement and 1.5 - 2× root mean squared error (RMSE) reduction when applied to GRAPPA and improves robustness to ACS size for various acceleration rates in comparison to other scan-specific techniques. When applied to advanced reconstruction techniques such as residual-RAKI, 2D VC-GRAPPA and LORAKS, SPARK achieves up to 20% RMSE improvement. SPARK with 3D GRAPPA also improves RMSE performance by ~2×, SSIM performance, and perceived image quality without a fully sampled ACS region. Finally, SPARK synergizes with non-Cartesian, 2D and 3D wave-encoding imaging by reducing RMSE between 20% and 25% and providing qualitative improvements. CONCLUSION: SPARK synergizes with physics-based acquisition and reconstruction techniques to improve accelerated MRI by training scan-specific models to estimate and correct reconstruction errors in k-space.

Highly accelerated EPI with wave encoding and multi-shot simultaneous multislice imaging.

PURPOSE: To introduce wave-encoded acquisition and reconstruction techniques for highly accelerated EPI with reduced g-factor penalty and image artifacts. THEORY AND METHODS: Wave-EPI involves application of sinusoidal gradients during the EPI readout, which spreads the aliasing in all spatial directions, thereby taking better advantage of 3D coil sensitivity profiles. The amount of voxel spreading that can be achieved by the wave gradients during the short EPI readout period is constrained by the slew rate of the gradient coils and peripheral nerve stimulation monitor. We propose to use a "half-cycle" sinusoidal gradient to increase the amount of voxel spreading that can be achieved while respecting the slew and stimulation constraints. Extending wave-EPI to multi-shot acquisition minimizes geometric distortion and voxel blurring at high in-plane resolutions, while structured low-rank regularization mitigates shot-to-shot phase variations. To address gradient imperfections, we propose to use different point spread functions for the k-space lines with positive and negative polarities, which are calibrated with a FLEET-based reference scan. RESULTS: Wave-EPI enabled whole-brain single-shot gradient-echo (GE) and multi-shot spin-echo (SE) EPI acquisitions at high acceleration factors at 3T and was combined with g-Slider encoding to boost the SNR level in 1 mm isotropic diffusion imaging. Relative to blipped-CAIPI, wave-EPI reduced average and maximum g-factors by up to 1.21- and 1.37-fold at Rin × Rsms  = 3 × 3, respectively. CONCLUSION: Wave-EPI allows highly accelerated single- and multi-shot EPI with reduced g-factor and artifacts and may facilitate clinical and neuroscientific applications of EPI by improving the spatial and temporal resolution in functional and diffusion imaging.

Blip up-down acquisition for spin- and gradient-echo imaging (BUDA-SAGE) with self-supervised denoising enables efficient T2 , T2 *, para- and dia-magnetic susceptibility mapping.

PURPOSE: To rapidly obtain high resolution T2 , T2 *, and quantitative susceptibility mapping (QSM) source separation maps with whole-brain coverage and high geometric fidelity. METHODS: We propose Blip Up-Down Acquisition for Spin And Gradient Echo imaging (BUDA-SAGE), an efficient EPI sequence for quantitative mapping. The acquisition includes multiple T2 *-, T2 '-, and T2 -weighted contrasts. We alternate the phase-encoding polarities across the interleaved shots in this multi-shot navigator-free acquisition. A field map estimated from interim reconstructions was incorporated into the joint multi-shot EPI reconstruction with a structured low rank constraint to eliminate distortion. A self-supervised neural network (NN), MR-Self2Self (MR-S2S), was used to perform denoising to boost SNR. Using Slider encoding allowed us to reach 1 mm isotropic resolution by performing super-resolution reconstruction on volumes acquired with 2 mm slice thickness. Quantitative T2 (=1/R2 ) and T2 * (=1/R2 *) maps were obtained using Bloch dictionary matching on the reconstructed echoes. QSM was estimated using nonlinear dipole inversion on the gradient echoes. Starting from the estimated R2 /R2 * maps, R2 ' information was derived and used in source separation QSM reconstruction, which provided additional para- and dia-magnetic susceptibility maps. RESULTS: In vivo results demonstrate the ability of BUDA-SAGE to provide whole-brain, distortion-free, high-resolution, multi-contrast images and quantitative T2 /T2 * maps, as well as yielding para- and dia-magnetic susceptibility maps. Estimated quantitative maps showed comparable values to conventional mapping methods in phantom and in vivo measurements. CONCLUSION: BUDA-SAGE acquisition with self-supervised denoising and Slider encoding enables rapid, distortion-free, whole-brain T2 /T2 * mapping at 1 mm isotropic resolution under 90 s.

Estrogen Regulates the Expression and Localization of YAP in the Uterus of Mice.

The dynamics of uterine endometrium is important for successful establishment and maintenance of embryonic implantation and development, along with extensive cell differentiation and proliferation. The tissue event is precisely and complicatedly regulated as several signaling pathways are involved including two main hormones, estrogen and progesterone signaling. We previously showed a novel signaling molecule, Serine/threonine protein kinase 3/4 (STK3/4), which is responded to hormone in the mouse uterine epithelium. However, the role and regulation of its target, YES-associated protein (YAP) remains unknown. In this study, we investigated the expression and regulation of YAP in mouse endometrium. We found that YAP was periodically expressed in the endometrium during the estrous cycle. Furthermore, periodic expression of YAP was shown to be related to the pathway under hormone treatment. Interestingly, estrogen was shown to positively modulate YAP via endometrial epithelial receptors. In addition, the knockdown of YAP showed that YAP regulated various target genes in endometrial cells. The knockdown of YAP down-regulated numerous targets including ADAMTS1, AMOT, AMOTL1, ANKRD1, CTNNA1, MCL1. On the other hand, the expressions of AREG and AXL were increased by its knockdown. These findings imply that YAP responds via Hippo signaling under various intrauterine signals and is considered to play a role in the expression of factors important for uterine endometrium dynamic regulation.

Toll-like receptors: A pathway alluding to cancer control.

Toll-like receptors (TLRs) are usually expressed on immune cells such as macrophages, dendritic cells, mast cells, as well as on eosinophils and some epithelial cells. They play a central role in the recognition of harmful molecules that belong to invading microorganisms or internal damaged tissues, which lead to inflammation. Among the hallmarks of cancer, there is immune evasion and inflammation. Summing this with the discovery that a majority of cancers also seem to express TLRs, made researchers realize these receptors might also be linked with cancer progression. This review will cover some of the effects of TLR engagement in cancer cells that might induce the promotion or inhibition of cancer with mechanisms involved. The differences of TLR expression in cancer progression and its possible relation with patient prognosis, TLR genetic disorders found in cancer, and new strategies to cancer therapy will be discussed to target TLRs in cancer cells.

Characterization of canine adipose tissue-derived mesenchymal stem cells immortalized by SV40-T retrovirus for therapeutic use.

Canine mesenchymal stem cells (cMSCs) are gaining popularity in the veterinary field as a regenerative therapy. But, their limited culture lifespan makes it an obstacle for preclinical investigation and therapeutic use. In this study, primary canine adipose tissue-derived MSCs (PCAT-MSCs) were isolated from adipose tissue and were transfected with the SV40-T retrovirus resulting in a life-extended immortalized canine adipose tissue-derived MSCs (ICAT-MSCs). A comparison was made through the characterization of both PCAT-MSCs and ICAT-MSCs. Both showed a fibroblastic morphology; ICAT-MSCs showed a higher potential of colony formation compared with PCAT-MSCs and a reduced population doubling time; stem cell markers SOX2 and NANOG were expressed in both cell lines; karyotyping analysis showed no abnormalities in both PCAT-MSCs and ICAT-MSCs; both cell lines were CD90+ , CD44 + , and CD45 - ; both generated chondrogenic pellet; in osteogenic differentiation both showed upregulation of Osterix, a master transcriptome of osteogenesis, but in PCAT-MSCs, an upregulation of SOX2 was also observed. In conclusion, ICAT-MSCs showed similar characteristics with PCAT-MSCs, thus established as an easy to access platform for studies on better understanding about cMSCs nature.

Robust water-fat separation for multi-echo gradient-recalled echo sequence using convolutional neural network.

PURPOSE: To accurately separate water and fat signals for bipolar multi-echo gradient-recalled echo sequence using a convolutional neural network (CNN). METHODS: A CNN architecture was designed and trained using the relationship between multi-echo images from the bipolar multi-echo gradient-recalled echo sequence and artifact-free water-fat-separated images. The artifact-free water-fat-separated images for training the CNN were obtained from multiple signals with different TEs by using iterative decomposition of water and fat with echo asymmetry and the least-squares estimation method, in which multiple signals at different TEs were acquired using a single-echo gradient-recalled echo sequence. We also proposed a data augmentation method using a synthetic field inhomogeneity to generate multi-echo signals, including various bipolar multi-echo gradient-recalled echo artifacts so that the CNN could prevent overfitting and increase the separation accuracy. We trained the CNN using in vivo knee images and tested it using in vivo knee, head, and ankle images. RESULTS: In vivo imaging results showed that the proposed CNN could separate water-fat images accurately. Although the proposed CNN was trained using only in vivo knee images, the proposed CNN could also separate water-fat images of different imaging regions. The proposed data augmentation method could prevent overfitting even with a limited number of training data sets and make the method robust to magnetic field inhomogeneities. CONCLUSION: The proposed CNN could obtain water-fat-separated images from the multi-echo images acquired from the bipolar multi-echo gradient-recalled echo sequence, which included artifacts from the bipolar gradients.

Non-contrast-enhanced peripheral MR angiography using velocity-selective excitation.

PURPOSE: To develop a new non-contrast-enhanced peripheral MR angiography that provides a high contrast angiogram without using electrocardiography triggering and saturation radiofrequency pulses. METHODS: A velocity-selective excitation technique is used in conjunction with the golden-angle radial sampling scheme. The signal amplitude varies according to the velocity of the flow by the velocity-selective excitation technique. Because the arterial blood velocity varies depending on the cardiac phase, the acquired data can be classified into systolic and diastolic phase based on the signal amplitude of the artery. Two images are then reconstructed from the systolic and diastolic phase data, respectively, and an image reflecting the differences between the two images is obtained to eliminate background and vein signals. The performance of the proposed method was compared with the quiescent-interval single shot (QISS) in eight healthy subjects and an elderly subject. RESULTS: The proposed method generated fewer residual venous and background signals than the QISS. Furthermore, the maximum intensity projection images, the relative contrast, and the apparent contrast-to-noise ratio results showed that the proposed method produced a better contrast than the QISS. CONCLUSIONS: The proposed non-contrast-enhanced peripheral MR angiography technique can provide a high contrast angiogram without the use of electrocardiography triggering and saturation radiofrequency pulses. Magn Reson Med 79:779-788, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Postural stability in patients with anterior cruciate ligament tears with and without medial meniscus tears.

PURPOSE: To compare postural stability in patients with isolated anterior cruciate ligament (ACL) tears and ACL tears with associated meniscal tears. METHODS: Quadriceps and hamstring muscle strength and their ratio, as well as the relationships of these parameters with postural stability, were compared in 23 patients with isolated ACL tears and 27 with combined ACL and medial meniscus tears. Postural stability was determined from the anterior-posterior, medial-lateral, and overall stability indices using the Biodex Stability System. RESULTS: On both the involved and uninvolved sides, there were no differences in mean stability indices, including anterior-posterior, medial-lateral, and overall stability indices, in patients with isolated and combined ACL tears. In patients with isolated ACL tears, both overall (2.3 ± 1.2 vs. 1.8 ± 1.4, p = 0.033) and medial-lateral (1.2 ± 0.6 vs. 1.0 ± 0.5, p = 0.031) stability indices were significantly higher on the involved compared to the uninvolved side. These differences, however, were not observed in the combined ACL tear group. CONCLUSION: No significant differences in postural instability on the affected and unaffected sides were observed in patients with isolated ACL tears and those with combined ACL and medial meniscus tears. These findings indicate that there is no need to reduce the goal of restoring proprioception in patients with combined compared with isolated ACL tears. LEVEL OF EVIDENCE: III.

Paradoxical effects of human adipose tissue-derived mesenchymal stem cells on progression of experimental arthritis in SKG mice.

We evaluated the therapeutic effect of human adipose tissue-derived mesenchymal stem cells (hAd-MSCs) in a SKG arthritis model, a relevant animal model for human rheumatoid arthritis. hAd-MSCs were administered intraperitoneally into the mice for five consecutive days from on day 12 or 34 after arthritis induction, when the average clinical score was 0.5 or 5, respectively. They remarkably suppressed arthritis when administered on day 12. Disease suppression was correlated with reduction of pro-inflammatory cytokines and with increased levels of TGF-ß and IL-10 from splenocytes. However, when hAd-MSCs were administered on day 34, the clinical scores were not improved, the histopathological scores were aggravated, and cytokine profiles were differed. Thus, hAd-MSCs showed paradoxical effects, according to the disease phase when they were administered. These suggest that the same cells acted differently depending on the disease progress, and cautions should be paid for safe and effective use of MSCs.

PRIME: Phase Reversed Interleaved Multi-Echo acquisition enables highly accelerated distortion-free diffusion MRI.

PURPOSE: To develop and evaluate a new pulse sequence for highly accelerated distortion-free diffusion MRI (dMRI) by inserting an additional echo without prolonging TR, when generalized slice dithered enhanced resolution (gSlider) radiofrequency encoding is used for volumetric acquisition. METHODS: A phase-reversed interleaved multi-echo acquisition (PRIME) was developed for rapid, high-resolution, and distortion-free dMRI, which includes two echoes where the first echo is for target diffusion-weighted imaging (DWI) acquisition with high-resolution and the second echo is acquired with either 1) lower-resolution for high-fidelity field map estimation, or 2) matching resolution to enable efficient diffusion relaxometry acquisitions. The sequence was evaluated on in vivo data acquired from healthy volunteers on clinical and Connectome 2.0 scanners. RESULTS: In vivo experiments demonstrated that 1) high in-plane acceleration (Rin-plane of 5-fold with 2D partial Fourier) was achieved using the high-fidelity field maps estimated from the second echo, which was made at a lower resolution/acceleration to increase its SNR while matching the effective echo spacing of the first readout, 2) high-resolution diffusion relaxometry parameters were estimated from dual-echo PRIME data using a white matter model of multi-TE spherical mean technique (MTE-SMT), and 3) high-fidelity mesoscale DWI at 550 um isotropic resolution could be obtained in vivo by capitalizing on the high-performance gradients of the Connectome 2.0 scanner. CONCLUSION: The proposed PRIME sequence enabled highly accelerated, high-resolution, and distortion-free dMRI using an additional echo without prolonging scan time when gSlider encoding is utilized.

Comparison of the ultrastructural and immunophenotypic characteristics of human umbilical cord-derived mesenchymal stromal cells and in situ cells in Wharton's jelly.

The umbilical cord contains mucinous connective tissue, called Wharton's jelly. It consists of stromal cells, collagen fibers, and amorphous ground substances composed of proteoglycan. Recently, these stromal cells have been redefined as a new cell therapy source, named human umbilical cord-derived mesenchymal stromal cells (hUCMSCs). However, there are few studies on the ultrastructural features and immune-phenotypic characteristics of isolated hUCMSCs and comparisons with the cells found in original cord tissues. In this study, the authors describe and compare the phenotypic characteristics of hUCMSCs with cells in the umbilical cord in order to know the kinds of cells and ultrastructural changes. Isolated hUCMSCs showed similar ultrastructure with few structural differences from in situ stromal cells, and they are relatively homogenous and well-developed mesenchymal cells that demonstrate a myofibroblastic phenotype.

Comparison of Cryopreservation Media for Mesenchymal Stem Cell Spheroids.

Multipotent mesenchymal stromal/stem cell (MSC) spheroids generated in three-dimensional culture are of considerable interest as a novel therapeutic tool for regenerative medicine. However, the lack of reliable methods for storing MSC spheroids represents a significant roadblock to their successful use in the clinic. An ideal storage medium for MSC spheroids should function as both a vehicle for delivery and a cryoprotectant during storage of spheroids for use at a later time. In this study, we compared the outcomes after subjecting MSC spheroids to a freeze/thaw cycle in three Good Manufacturing Practices-grade cryopreservation media, CryoStor10 (CS10), Stem-Cellbanker (SCB), and Recovery Cell Culture Freezing Media (RFM) or conventional freezing medium (CM) (CM, Dulbecco's modified Eagle's medium containing 20% fetal bovine serum and 10% dimethyl sulfoxide) as a control for 2 months. The endpoints tested were viability, morphology, and expression of stem cell markers and other relevant genes. The results of LIVE/DEAD™ assays and annexin V/propidium iodide staining suggested that viability was relatively higher after one freeze/thaw cycle in CS10 or SCB than after freeze/thaw in CM or RFM. Furthermore, the relative "stemness" and expression of MSC markers were similar with or without freeze/thaw in CS10. Scanning electron microscopy also indicated that the surface morphology of MSC spheroids was well preserved after cryopreservation in CS10. Thus, even though it was tested for a short-term period, we suggest that CS10, which has been approved for clinical use by the U.S. Food and Drug Association, is a promising cryopreservation medium that would facilitate the development of MSC spheroids for future clinical use.

Self-assembled adipose-derived mesenchymal stem cells as an extracellular matrix component- and growth factor-enriched filler.

The clinical application of mesenchymal stem cells (MSCs) is attracting attention due to their excellent safety, convenient acquisition, multipotency, and trophic activity. The clinical effectiveness of transplanted MSCs is well-known in regenerative and immunomodulatory medicine, but there is a demand for their improved viability and regenerative function after transplantation. In this study, we isolated MSCs from adipose tissue from three human donors and generated uniformly sized MSC spheroids (∼100 µm in diameter) called microblocks (MiBs) for dermal reconstitution. The viability and MSC marker expression of MSCs in MiBs were similar to those of monolayer MSCs. Compared with monolayer MSCs, MiBs produced more extracellular matrix (ECM) components, including type I collagen, fibronectin, and hyaluronic acid, and growth factors such as vascular endothelial growth factor and hepatocyte growth factor. Subcutaneously injected MiBs showed skin volume retaining capacity in mice. These results indicate that MiBs could be applied as regenerative medicine for skin conditions such as atrophic scar by having high ECM and bioactive factor expression.

Wave-Encoded Model-Based Deep Learning for Highly Accelerated Imaging with Joint Reconstruction.

A recently introduced model-based deep learning (MoDL) technique successfully incorporates convolutional neural network (CNN)-based regularizers into physics-based parallel imaging reconstruction using a small number of network parameters. Wave-controlled aliasing in parallel imaging (CAIPI) is an emerging parallel imaging method that accelerates imaging acquisition by employing sinusoidal gradients in the phase- and slice/partition-encoding directions during the readout to take better advantage of 3D coil sensitivity profiles. We propose wave-encoded MoDL (wave-MoDL) combining the wave-encoding strategy with unrolled network constraints for highly accelerated 3D imaging while enforcing data consistency. We extend wave-MoDL to reconstruct multicontrast data with CAIPI sampling patterns to leverage similarity between multiple images to improve the reconstruction quality. We further exploit this to enable rapid quantitative imaging using an interleaved look-locker acquisition sequence with T2 preparation pulse (3D-QALAS). Wave-MoDL enables a 40 s MPRAGE acquisition at 1 mm resolution at 16-fold acceleration. For quantitative imaging, wave-MoDL permits a 1:50 min acquisition for T1, T2, and proton density mapping at 1 mm resolution at 12-fold acceleration, from which contrast-weighted images can be synthesized as well. In conclusion, wave-MoDL allows rapid MR acquisition and high-fidelity image reconstruction and may facilitate clinical and neuroscientific applications by incorporating unrolled neural networks into wave-CAIPI reconstruction.

Enzymatically labeled chromosomal probes for in situ identification of human cells in xenogeneic transplant models.

Analysis of the viability, differentiation, clonogenicity and function of human stem/progenitor cells requires suitable xenograft models. However, the identification of transplanted cells has been generally difficult. Fluorescence in situ hybridization is a tedious method for analyzing tissues, and localization of transplanted cells with X or Y chromosome probes is limited by the sparse signals produced. Therefore, we examined the possibility of generating either pan-nuclear signals with a total human DNA probe or multiple nuclear signals with a pan-centromeric human DNA probe. The probes were labeled with digoxigenin to make reaction products visible by light microscopy and to allow the use of immunohistochemistry methods incorporating various color schemes to demonstrate specific properties of transplanted cells. The ability to localize all types of nucleated human cells with such probes will facilitate studies of stem cell biology and cell and gene therapy, as well as the development of new animal models.

Both CD45RA+ and CD45RO+ human CD4+ T cells drive direct xenogeneic T-cell responses against porcine aortic endothelial cells.

BACKGROUND: Xenogeneic cellular immune responses are mediated by either direct or indirect pathways depending on the participation of donor or host antigen presenting cells, respectively. The contribution of direct response of human T cells, especially memory T cells, to porcine antigen presenting cells is currently unknown. Here, we sought to determine whether human peripheral blood memory/activated phenotype T cells are directly responsive to porcine endothelial cells. METHODS: Porcine aortic endothelial cells (PAECs) were prepared from Yorkshire or miniature pigs. Highly purified human T cells, including naïve and memory/activated phenotype cells, were incubated with PAECs with or without the addition of exogenous cytokines. T-cell proliferation and T-cell receptor (TCR) Vbeta usage in response to PAECs were analyzed. RESULTS: Both CD8(+) and CD4(+) T cells responded directly to PAECs and exhibited exclusive responsiveness to SLA class I and class II molecules, respectively. Naïve and memory/activated phenotype CD4(+) T cells responded against PAECs, whereas only naïve phenotype CD8(+) T cells contributed to such a response. In addition, both populations of xenogeneic human CD4(+) T cells exhibited similar and diverse V beta usage. CONCLUSION: Due to the considerable contribution of human CD45RO(+)CD4(+) T cells to the xenoreactivity against PAECs, effective control of xenogeneic memory/activated T-cell responses would significantly affect long-term survival of transplanted grafts.