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.

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.

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.

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.

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.

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.

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.

Human Stem Cell Responses and Surface Characteristics of 3D Printing Co-Cr Dental Material.

Recently, the selective laser melting (SLM) method of manufacturing three dimensional (3D) dental prosthetics by applying a laser to metal powder has been widely used in the field of dentistry. This study investigated human adipose derived stem cell (hADSC) behavior on a 3D printed cobalt-chrome (Co-Cr) alloy and its surface characteristics and compared them those of a nickel-chrome (Ni-Cr) alloy. Alloys were divided into four groups according to the material and manufacturing methods. Co-Cr disks were manufactured with three different methods: a conventional casting method, a metal milling method, and an SLM method. Ni-Cr disks were manufactured with a conventional casting method. The surface roughness and compositions of the disks were assessed. hADSCs were then cultured on the disks. Cell morphologies on the disks were analyzed by a field emission scanning electron microscope (FE-SEM). Cell proliferation was assessed with a bromodeoxyuridine (BrdU) assay kit. Cell viability was evaluated with a water-soluble tetrazolium salt (WST) assay kit. There were no differences in surface roughness between all groups. The cells were well attached to the disks, and morphologies of the cells were similar. The cell proliferation and viability of the Ni-Cr disks were significantly lower than the other groups. However, the Co-Cr disks showed no differences in their different fabricating methods. In conclusion, the biocompatibility of 3D printed Co-Cr alloys showed comparable results compared to that of the conventional casting method, and these alloys were more biocompatible than Ni-Cr alloys.

Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis.

Endothelin-1 (ET-1) induces contraction, proliferation, and collagen synthesis of activated hepatic stellate cells and is a potent mediator of portal hypertension. Endothelin-converting enzyme-1 (ECE-1) generates ET-1 from the inactive precursor big-endothelin-1. The cellular distribution and activity of ECE-1 in the liver is unknown. Hepatic fibrogenesis was induced in rats by CCl4 administration and secondary biliary cirrhosis after 6 weeks of complete bile duct occlusion (BDO). The tissue ET-1 and ET receptor protein levels were quantified, the ECE-1 isoform mRNAs were measured by RNase protection assay and ECE-1 activity was analyzed. ECE-1a and -b mRNA were upregulated in biliary cirrhosis and in CCl4-injured livers, whereas ECE-1c mRNA remained unchanged. ECE-1 activity was increased after BDO and peaked at 12 h after acute CCl4-intoxication. Tissue levels of ET-1, ETA- and ETB receptors were elevated 7-, 5-, and 4.6-fold in cirrhotic rats, respectively. ECE-1 activity increased following BDO and acute CCl4-intoxication. In conclusion, ECE-1a and -b RNAs are upregulated in fibrogenesis, indicating that these isoforms play a central role in ET-1 generation during fibrogenesis and portal hypertension.

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 and Differentiation of Circulating Blood Mesenchymal Stem Cells and the Role of Phosphatidylinositol 3-Kinase in Modulating the Adhesion.

Bone marrow mesenchymal stem cells (BM MSCs) can differentiate into multi-lineage tissues. However, obtaining BM MSCs by aspiration is difficult and can be painful; therefore peripheral blood (PB) MSCs might provide an easier alternative for clinical applications. Here, we show that circulating PB MSCs proliferate as efficiently as BM MSCs in the presence of extracellular matrix (ECM) and that differentiation potential into osteoblast in vitro and in vivo. Both BM MSCs and PB MSCs developed into new bone when subcutaneously transplanted into immune-compromised mice using hydroxyapatite/tricalcium phosphate as a carrier. Furthermore, LY294002 and Wortmannin blocked mesenchymal stem cell attachment in a dose-dependent manner, suggesting a role of phosphatidylinositol 3-kinase in MSC attachment. Our data showed that the growth of PB MSCs could be regulated by interaction with the ECM and that these cells could differentiate into osteoblasts, suggesting their potential for clinical applications.

Osteoclastogenesis Behavior of Zirconia for Dental Implant.

Zirconia is worth studying as an alternative to dental titanium implants to overcome the disadvantages of titanium. This study investigated the surface characteristics of the zirconia implant material and osteoclastogenesis responses on the surface compared with titanium. Yttrium oxide-stabilized 5% tetragonal zirconia polycrystalline specimens were manufactured, and osteoclast-precursor cells were cultured and differentiated into osteoclasts on the specimens. Surface shape, roughness, and chemical composition were evaluated. After culturing, cell morphologies and differentiation capacity were analyzed using tartrate-resistant acid phosphatase activity (TRACP). mRNA of two critical transcription factors, nuclear factor of activated T-cells 1 (NFATc1) and c-Fos were measured, and protein levels of NFATc1 and c-Fos were investigated. The zirconia specimens had rhomboid-like shapes with smooth surfaces and exhibited no difference in surface roughness compared to the titanium specimens. Morphologies of differentiated osteoclasts on both materials were similar. TRACP activity on the zirconia showed comparable results to that on the titanium. The mRNA value of NFATc1 on the zirconia was higher than that on the titanium at day four. The protein level of c-Fos was expressed thicker on the zirconia when compared to the titanium at day two. The results of this study suggest that zirconia material provides adequate osteoclastogenesis behaviors for dental implant use.

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.

Isokinetic knee strength and proprioception before and after anterior cruciate ligament reconstruction: A comparison between home-based and supervised rehabilitation.

BACKGROUND: Rehabilitation after anterior cruciate ligament (ACL) reconstruction focuses on restoring knee deficiencies and function. However, the extent of the clinician's direct supervision that is required to recover knee function is unknown. OBJECTIVE: To investigate differences in isokinetic knee strength improvement, endurance, and proprioception between home-based (HBR) and supervised rehabilitation (SR). METHODS: Thirty participants were randomly allocated to each group after reconstruction. Isokinetic knee strength and proprioception were measured using the Biodex multi-joint and stability systems, respectively, before and after intervention. RESULTS: The SR group showed a significant improvement from baseline, but not the HBR group (SR group, from 1.94 ± 1.44 to 1.02 ± 0.92, p< 0.05; HBR group, from 1.69 ± 0.88 to 1.61 ± 0.90, p> 0.05). There was a significant effect of exercise type on proprioception scores after controlling for pretest values (p< 0.05). No significant difference in isokinetic knee strength was observed between the groups. CONCLUSIONS: HBR recovered knee strength as effectively as the SR, but SR was more effective than HBR for the recovery of proprioception and functional knee movement. This result indicates that guidance from health professionals play an important role in enhancing proprioception for patients following ACL reconstruction.

Technical Note: Interleaved bipolar acquisition and low-rank reconstruction for water-fat separation in MRI.

PURPOSE: To acquire interleaved bipolar data and reconstruct the full data using low-rank property for water-fat separation. METHODS: Bipolar acquisition suffers from issues related to gradient switching, the opposite gradient polarities, and other system imperfections, which prevent accurate water-fat separation. In this study, an interleaved bipolar acquisition scheme and a low-rank reconstruction method were proposed to reduce issues from the bipolar gradients while achieving a short imaging time. The proposed interleaved bipolar acquisition scheme collects echo-time signals from both gradient polarities; however, the sequence increases the imaging time. To reduce the imaging time, the signals were subsampled at every dimension of k-space. The low-rank property of the bipolar acquisition was defined and exploited to estimate the full data from the acquired subsampled data. To eliminate the bipolar issues, in the proposed method, the water-fat separation was performed separately for each gradient polarity, and the results for the positive and negative gradient polarities were combined after the water-fat separation. RESULTS: A phantom study and in vivo experiments were conducted on a 3T Siemens Verio system. The results for the proposed method were compared with the results of the fully sampled interleaved bipolar acquisition and the Soliman's method, which was the previous water-fat separation approach for reducing the issues of bipolar gradients and accelerating the interleaved bipolar acquisition. The proposed method provided accurate water and fat images without the issues of bipolar gradients and demonstrated a better performance compared with the results of the previous methods. CONCLUSIONS: The water-fat separation using the bipolar acquisition has several benefits including a short echo-spacing time. However, it suffers from bipolar-gradient issues such as strong gradient switching, system imperfection, and eddy current effects. This study demonstrated that accurate water-fat separated images can be obtained using the proposed interleaved bipolar acquisition and low-rank reconstruction by using the benefits of the bipolar acquisition while reducing the bipolar-gradient issues with a short imaging time.

A novel calcium-accumulating peptide/gelatin in situ forming hydrogel for enhanced bone regeneration.

Bioactive agents, including proteins and peptides, can be loaded into hydrogels to improve bone regenerative capacity with their controlled release. However, the current loading method has focused on physical mixing, which has limited release control. Therefore, alternative conjugation of bioactive agents with hydrogels is highly recommended. Direct chemical conjugation of synthetic peptides containing a functional moiety with a hydrogel would be ideal. Here, we synthesized a bioactive calcium accumulating peptide (CAP) containing a collagen binding motif, which can induce osteogenic differentiation. A tyrosine residue in CAP was used to directly chemically conjugate the peptide with a gelatin-based enzymatically crosslinked hydroxyphenyl propionic acid hydrogel under H2 O2 /Horse radish peroxidase conditions. To test the acceleration of bone formation, human periodontal ligament stem cells (PDLSCs) were loaded into a chemically conjugated CAP hydrogel. The CAP hydrogel induced bone mineralization around the PDLSCs and increased osteogenic marker expressions in vitro. It also recovered a bone layer in a calvarial defect 4 weeks postimplantation. In summary, an injectable CAP hydrogel scaffold system was developed as a potentially useful engineered microenvironment to enhance bone restoration, and it could be utilized as a vehicle for bioactive delivery of stem cells in tissue regenerative therapy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 531-542, 2018.