Publications by authors named "Wang Lv"

611 Publications

Photoacoustic Computed Tomography of Breast Cancer in Response to Neoadjuvant Chemotherapy.

Adv Sci (Weinh) 2021 04 23;8(7):2003396. Epub 2021 Feb 23.

Caltech Optical Imaging Laboratory Andrew and Peggy Cherng Department of Medical Engineering California Institute of Technology Pasadena CA 91125 USA.

Neoadjuvant chemotherapy (NAC) has contributed to improving breast cancer outcomes, and it would ideally reduce the need for definitive breast surgery in patients who have no residual cancer after NAC treatment. However, there is no reliable noninvasive imaging modality accepted as the routine method to assess response to NAC. Because of the inability to detect complete response, post-NAC surgery remains the standard of care. To overcome this limitation, a single-breath-hold photoacoustic computed tomography (SBH-PACT) system is developed to provide contrast similar to that of contrast-enhanced magnetic resonance imaging, but with much higher spatial and temporal resolution and without injection of contrast chemicals. SBH-PACT images breast cancer patients at three time points: before, during, and after NAC. The analysis of tumor size, blood vascular density, and irregularity in the distribution and morphology of the blood vessels on SBH-PACT accurately identifies response to NAC as confirmed by the histopathological diagnosis. SBH-PACT shows its near-term potential as a diagnostic tool for assessing breast cancer response to systemic treatment by noninvasively measuring the changes in cancer-associated angiogenesis. Further development of SBH-PACT may also enable serial imaging, rather than the use of current invasive biopsies, to diagnose and follow indeterminate breast lesions.
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http://dx.doi.org/10.1002/advs.202003396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025032PMC
April 2021

Snapshot photoacoustic topography through an ergodic relay of optical absorption in vivo.

Nat Protoc 2021 May 12;16(5):2381-2394. Epub 2021 Apr 12.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA.

Photoacoustic tomography (PAT) has demonstrated versatile biomedical applications, ranging from tracking single cells to monitoring whole-body dynamics of small animals and diagnosing human breast cancer. Currently, PAT has two major implementations: photoacoustic computed tomography (PACT) and photoacoustic microscopy (PAM). PACT uses a multi-element ultrasonic array for parallel detection, which is relatively complex and expensive. In contrast, PAM requires point-by-point scanning with a single-element detector, which has a limited imaging throughput. The trade-off between the system cost and throughput demands a new imaging method. To this end, we have developed photoacoustic topography through an ergodic relay (PATER). PATER can capture a wide-field image with only a single-element ultrasonic detector upon a single laser shot. This protocol describes the detailed procedures for PATER system construction, including component selection, equipment setup and system alignment. A step-by-step guide for in vivo imaging of a mouse brain is provided as an example application. Data acquisition, image reconstruction and troubleshooting procedures are also elaborated. It takes ~130 min to carry out this protocol, including ~60 min for both calibration and snapshot wide-field data acquisition using a laser with a 2-kHz pulse repetition rate. PATER offers low-cost snapshot wide-field imaging of fast dynamics, such as visualizing blood pulse wave propagation and tracking melanoma tumor cell circulation in mice in vivo. We envision that PATER will have wide biomedical applications and anticipate that the compact size of the setup will allow it to be further developed as a wearable device to monitor human vital signs.
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http://dx.doi.org/10.1038/s41596-020-00487-wDOI Listing
May 2021

CircRNA_100395 Carried by Exosomes From Adipose-Derived Mesenchymal Stem Cells Inhibits the Malignant Transformation of Non-Small Cell Lung Carcinoma Through the miR-141-3p-LATS2 Axis.

Front Cell Dev Biol 2021 25;9:663147. Epub 2021 Mar 25.

Department of Medical Oncology, Shulan (Hangzhou) Hospital, Affiliated to Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China.

Objective: The specific purpose of this study is to investigate the impact exosomes from adipose-derived mesenchymal stem cell (AMSC) has on non-small cell lung carcinoma (NSCLC) and the relative applications.

Methods: circ_100395, miR-141-3p, and LATS2 were expressed and detected in NSCLC and paracancerous tissues as well as NSCLC cell lines. Pearson correlation analysis, Dual-Luciferase Reporter Assay and RNA pull-down assay were used to validate their expression and interaction, respectively. After isolation and culture of AMSCs, exosomes were extracted and identified. EdU, epithelial-mesenchymal transition (EMT), and cell colony formation assay were used to distinguish the biological activity of the cells. Expression Hippo/YAP signalling pathway-related proteins were measured by western blotting. Subsequently, tumour volume and weight were confirmed based on xenograft nude mice models, Ki-67 and LATS2 expression was observed by immunohistochemistry.

Results: circ_100395 was lowly expressed in NSCLC tissues or cells. The negative correlations and interactions were confirmed between circ_100395 and miR-141-3p, miR-141-3p, and LATS2. AMSC-derived exosomes with overexpression of circ_100395 (exo-circ_100395) significantly inhibited the biological activity as well as EMT of H1650 cells and Hippo/YAP signalling pathway activity. In addition, exo-circ_100395 markedly reduced tumour volume and weight as well as Ki-67 and LASP1 expression . However, overexpressed miR-141-3p or knocked down LATS2 alleviated the above effects.

Conclusion: Exo-circ_100395 can increase LATS2 expression by sponging miR-141-3p to regulate Hippo/YAP signalling pathway, thereby inhibiting NSCLC malignant transformation.
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http://dx.doi.org/10.3389/fcell.2021.663147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027360PMC
March 2021

Toward photoswitchable electronic pre-resonance stimulated Raman probes.

J Chem Phys 2021 Apr;154(13):135102

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

Reversibly photoswitchable probes allow for a wide variety of optical imaging applications. In particular, photoswitchable fluorescent probes have significantly facilitated the development of super-resolution microscopy. Recently, stimulated Raman scattering (SRS) imaging, a sensitive and chemical-specific optical microscopy, has proven to be a powerful live-cell imaging strategy. Driven by the advances of newly developed Raman probes, in particular the pre-resonance enhanced narrow-band vibrational probes, electronic pre-resonance SRS (epr-SRS) has achieved super-multiplex imaging with sensitivity down to 250 nM and multiplexity up to 24 colors. However, despite the high demand, photoswitchable Raman probes have yet to be developed. Here, we propose a general strategy for devising photoswitchable epr-SRS probes. Toward this goal, we exploit the molecular electronic and vibrational coupling, in which we switch the electronic states of the molecules to four different states to turn their ground-state epr-SRS signals on and off. First, we showed that inducing transitions to both the electronic excited state and triplet state can effectively diminish the SRS peaks. Second, we revealed that the epr-SRS signals can be effectively switched off in red-absorbing organic molecules through light-facilitated transitions to a reduced state. Third, we identified that photoswitchable proteins with near-infrared photoswitchable absorbance, whose states are modulable with their electronic resonances detunable toward and away from the pump photon energy, can function as the photoswitchable epr-SRS probes with desirable sensitivity (<1 µM) and low photofatigue (>40 cycles). These photophysical characterizations and proof-of-concept demonstrations should advance the development of novel photoswitchable Raman probes and open up the unexplored Raman imaging capabilities.
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http://dx.doi.org/10.1063/5.0043791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019356PMC
April 2021

Multifocal photoacoustic microscopy using a single-element ultrasonic transducer through an ergodic relay.

Light Sci Appl 2020 Jul 31;9(1):135. Epub 2020 Jul 31.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA, 91125, USA.

Optical-resolution photoacoustic microscopy (OR-PAM) has demonstrated high-spatial-resolution imaging of optical absorption in biological tissue. To date, most OR-PAM systems rely on mechanical scanning with confocally aligned optical excitation and ultrasonic detection, limiting the wide-field imaging speed of these systems. Although several multifocal OR-PA (MFOR-PA) systems have attempted to address this limitation, they are hindered by the complex design in a constrained physical space. Here, we present a two-dimensional (2D) MFOR-PAM system that utilizes a 2D microlens array and an acoustic ergodic relay. Using a single-element ultrasonic transducer, this system can detect PA signals generated from 400 optical foci in parallel and then raster scan the optical foci patterns to form an MFOR-PAM image. This system improves the imaging resolution of an acoustic ergodic relay system from 220 to 13 μm and enables 400-folds shorter scanning time than that of a conventional OR-PAM system at the same resolution and laser repetition rate. We demonstrated the imaging ability of the system with both in vitro and in vivo experiments.
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http://dx.doi.org/10.1038/s41377-020-00372-xDOI Listing
July 2020

A five-m6A regulatory gene signature is a prognostic biomarker in lung adenocarcinoma patients.

Aging (Albany NY) 2021 Mar 26;13(7):10034-10057. Epub 2021 Mar 26.

Department of Thoracic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

We analyzed the prognostic value of N6-methyladenosine (m6A) regulatory genes in lung adenocarcinoma (LADC) and their association with tumor immunity and immunotherapy response. Seventeen of 20 m6A regulatory genes were differentially expressed in LDAC tissue samples from the TCGA and GEO databases. We developed a five-m6A regulatory gene prognostic signature based on univariate and Lasso Cox regression analysis. Western blot analysis confirmed that the five prognostic m6A regulatory proteins were highly expressed in LADC tissues. We constructed a nomogram with five-m6A regulatory gene prognostic risk signature and AJCC stages. ROC curves and calibration curves showed that the nomogram was well calibrated and accurately distinguished high-risk and low-risk LADC patients. Weighted gene co-expression analysis showed significant correlation between prognostic risk signature genes and the turquoise module enriched with cell cycle genes. The high-risk LADC patients showed significantly higher PD-L1 levels, increased tumor mutational burden, and a lower proportion of CD8 T cells in the tumor tissues and improved response to immune checkpoint blockade therapy. These findings show that this five-m6A regulatory gene signature is a prognostic biomarker in LADC and that immune checkpoint blockade is a potential therapeutic option for high-risk LADC patients.
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http://dx.doi.org/10.18632/aging.202761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064222PMC
March 2021

Gensenoside Rg1 protects against lipopolysaccharide- and d-galactose-induced acute liver failure via suppressing HMGB1-mediated TLR4-NF-κB pathway.

Mol Cell Probes 2021 04 20;56:101706. Epub 2021 Feb 20.

Emergency Medicine, Wenzhou People's Hospital, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, China. Electronic address:

Aim: Acute liver failure (ALF) is a life-threatening acute liver injury (ALI) with high mortality. Gensenoside Rg1 (G-Rg1) effects on Lipopolysaccharide- (LPS-) and d-galactose-(D-gal-) induced ALI, but its effects on ALF remained unclear. This paper aimed to validate its possible efficacy on ALF prevention.

Methods: For in vivo studies, histological examination was performed using hematoxylin-eosin (H&E) staining, and alanine aminotransferase (ALT), aspartate aminotransminase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) contents were measured. Levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) were quantified via enzyme-linked immunosorbent assay (ELISA). Human bronchial epithelial cell line BEAS-2B was used for ALF model in vitro and its viability was measured by MTT assay. Expressions of high mobility group box 1 (HMGB1) and toll-like receptor 4-Nuclear Factor-κB (TLR4-NF-κB) pathway-related proteins were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed.

Results: G-Rg1 relieved LPS- and D-gal-induced hepatic injury, and reduced ALT, AST and MDA levels but upregulated SOD and GSH levels, with downregulation on TNF-α and IL-6 levels. Expressions of HMGB1, TLR4 and NF-κB pathway-related proteins were also down-regulated after G-Rg1 treatment both in vivo and in vitro, while BEAS-2B cell viability was increased. However, overexpressed HMGB1 reversed the effects of G-Rg1 treatment in vitro.

Conclusion: G-Rg1 had a protective effect against LPS- and D-gal-induced ALF both in vitro and in vivo, which might be related to inhibited HMGB1-mediated TLR4-NF-κB Pathway. These discoveries suggested that G-Rg1 could be a potential agent for prevention against ALF.
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http://dx.doi.org/10.1016/j.mcp.2021.101706DOI Listing
April 2021

A nomogram for predicting the risk of lymph node metastasis in T1-2 non-small-cell lung cancer based on PET/CT and clinical characteristics.

Transl Lung Cancer Res 2021 Jan;10(1):430-438

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Accurately predicting the risk level for a lymph node metastasis is critical in the treatment of non-small cell lung cancer (NSCLC). This study aimed to construct a novel nomogram to identify patients with a risk of lymph node metastasis in T1-2 NSCLC based on positron emission tomography/computed tomography (PET/CT) and clinical characteristics.

Methods: From January 2011 to November 2017, the records of 318 consecutive patients who had undergone PET/CT examination within 30 days before surgical resection for clinical T1-2 NSCLC were retrospectively reviewed. A nomogram to predict the risk of lymph node metastasis was constructed. The model was confirmed using bootstrap resampling, and an independent validation cohort contained 156 patients from June 2017 to February 2020 at another institution.

Results: Six factors [age, tumor location, histology, the lymph node maximum standardized uptake value (SUVmax), the tumor SUVmax and the carcinoembryonic antigen (CEA) value] were identified and entered into the nomogram. The nomogram developed based on the analysis showed robust discrimination, with an area under the receiver operating characteristic curve of 0.858 in the primary cohort and 0.749 in the validation cohort. The calibration curve for the probability of lymph node metastasis showed excellent concordance between the predicted and actual results. Decision curve analysis suggested that the nomogram was clinically useful.

Conclusions: We set up and validated a novel and effective nomogram that can predict the risk of lymph node metastasis for individual patients with T1-2 NSCLC. This model may help clinicians to make treatment recommendations for individuals.
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http://dx.doi.org/10.21037/tlcr-20-1026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867781PMC
January 2021

High-speed three-dimensional photoacoustic computed tomography for preclinical research and clinical translation.

Nat Commun 2021 02 9;12(1):882. Epub 2021 Feb 9.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, USA.

Photoacoustic computed tomography (PACT) has generated increasing interest for uses in preclinical research and clinical translation. However, the imaging depth, speed, and quality of existing PACT systems have previously limited the potential applications of this technology. To overcome these issues, we developed a three-dimensional photoacoustic computed tomography (3D-PACT) system that features large imaging depth, scalable field of view with isotropic spatial resolution, high imaging speed, and superior image quality. 3D-PACT allows for multipurpose imaging to reveal detailed angiographic information in biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualize whole brain vasculatures and hemodynamics. In the human breast, an in vivo imaging depth of 4 cm is achieved by scanning the breast within a single breath hold of 10 s. Here, we introduce the 3D-PACT system to provide a unique tool for preclinical research and an appealing prototype for clinical translation.
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http://dx.doi.org/10.1038/s41467-021-21232-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873071PMC
February 2021

Real-time observation and control of optical chaos.

Sci Adv 2021 Jan 13;7(3). Epub 2021 Jan 13.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering and Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Optical chaotic system is a central research topic due to its scientific importance and practical relevance in key photonic applications such as laser optics and optical communication. Because of the ultrafast propagation of light, all previous studies on optical chaos are based on either static imaging or spectral measurement, which shows only time-averaged phenomena. The ability to reveal real-time optical chaotic dynamics and, hence, control its behavior is critical to the further understanding and engineering of these systems. Here, we report a real-time spatial-temporal imaging of an optical chaotic system, using compressed ultrafast photography. The time evolution of the system's phase map is imaged without repeating measurement. We also demonstrate the ability to simultaneously control and monitor optical chaotic systems in real time. Our work introduces a new angle to the study of nonrepeatable optical chaos, paving the way for fully understanding and using chaotic systems in various disciplines.
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http://dx.doi.org/10.1126/sciadv.abc8448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806228PMC
January 2021

Metformin reverses chemoresistance in non-small cell lung cancer via accelerating ubiquitination-mediated degradation of Nrf2.

Transl Lung Cancer Res 2020 Dec;9(6):2337-2355

Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: The therapeutic efficacy of cisplatin-based chemotherapy for non-small cell lung cancer (NSCLC) is limited by drug resistance. In NSCLC, hyperactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) counteracts oxidative stress to promote chemoresistance. Metformin-mediated downregulation of Nrf2 plays a pivotal role in overcoming drug resistance in NSCLC cells. Therefore, a deeper understanding of the molecular mechanisms of combination therapy and the role of Nrf2 in chemotherapeutic response is critical to clinical translation.

Methods: The effects of combination therapy with metformin and cisplatin on cell proliferation and apoptosis, intracellular reactive oxygen species (ROS) levels, and xenograft tumor formation were analyzed in NSCLC cells. Co-immunoprecipitation (co-IP) and Phos-tag assays were used to explore the mechanism of metformin-mediated Nrf2 suppression. Immunohistochemical (IHC) staining was performed to detect Nrf2 expression in matched tumor samples before and after neoadjuvant chemotherapy.

Results: Metformin was observed to synergistically augment cisplatin-induced cytotoxicity by strongly inhibiting the level of Nrf2, thereby weakening the antioxidant system and detoxification ability of Nrf2 and enhancing ROS-mediated apoptosis in NSCLC. The synergistic antitumor effect of combination therapy is blocked by treatment with the ROS scavenger N-acetyl cysteine (NAC) as well as overexpression of Nrf2 and its downstream antioxidant protein. Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation. Moreover, for the first time, an association of non-decreased Nrf2 expression in patients after neoadjuvant chemotherapy with poor survival and chemoresistance in NSCLC was revealed.

Conclusions: Our findings illustrate the mechanism of metformin-mediated Nrf2 degradation through posttranslational modifications (PTMs), which weakens the ROS defense system in NSCLC. Fluctuations in Nrf2 expression have a strong predictive ability for chemotherapeutic response in neoadjuvant NSCLC patients. Targeting of the Nrf2 pathway could be a therapeutic strategy for overcoming chemoresistance, with metformin as the first choice for this strategy.
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http://dx.doi.org/10.21037/tlcr-20-1072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815349PMC
December 2020

Integration of Multitargeted Polymer-Based Contrast Agents with Photoacoustic Computed Tomography: An Imaging Technique to Visualize Breast Cancer Intratumor Heterogeneity.

ACS Nano 2021 02 19;15(2):2413-2427. Epub 2021 Jan 19.

Department of Chemistry & Biochemistry, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States.

One of the primary challenges in breast cancer diagnosis and treatment is intratumor heterogeneity (ITH), .., the coexistence of different genetically and epigenetically distinct malignant cells within the same tumor. Thus, the identification of ITH is critical for designing better treatments and hence to increase patient survival rates. Herein, we report a noninvasive hybrid imaging technology that integrates multitargeted and multiplexed patchy polymeric photoacoustic contrast agents (MTMPPPCAs) with single-impulse panoramic photoacoustic computed tomography (SIP-PACT). The target specificity ability of MTMPPPCAs to distinguish estrogen and progesterone receptor-positive breast tumors was demonstrated through both fluorescence and photoacoustic measurements and validated by tissue pathology analysis. This work provides the proof-of-concept of the MTMPPPCAs/SIP-PACT system to identify ITH in nonmetastatic tumors, with both high molecular specificity and real-time detection capability.
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http://dx.doi.org/10.1021/acsnano.0c05893DOI Listing
February 2021

Nrf2 Mediates Metabolic Reprogramming in Non-Small Cell Lung Cancer.

Front Oncol 2020 26;10:578315. Epub 2020 Nov 26.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Nuclear factor erythroid-2-related factor-2 (NFE2L2/Nrf2) is a transcription factor that regulates the expression of antioxidant genes. Both Kelch-like ECH-associated protein 1 (Keap1) mutations and Nrf2 mutations contribute to the activation of Nrf2 in non-small cell lung cancer (NSCLC). Nrf2 activity is associated with poor prognosis in NSCLC. Metabolic reprogramming represents a cancer hallmark. Increasing studies reveal that Nrf2 activation promotes metabolic reprogramming in cancer. In this review, we discuss the underlying mechanisms of Nrf2-mediated metabolic reprogramming and elucidate its role in NSCLC. Inhibition of Nrf2 can alter metabolic processes, thus suppress tumor growth, prevent metastasis, and increase sensitivity to chemotherapy in NSCLC. In conclusion, Nrf2 may serve as a therapeutic target for the treatment of NSCLC.
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http://dx.doi.org/10.3389/fonc.2020.578315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726415PMC
November 2020

A Novel Tubeless Urinary Catheter Protocol Enhanced Recovery After Minimally Invasive Lung Surgery.

Front Surg 2020 9;7:584578. Epub 2020 Nov 9.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Although previous studies have shown the feasibility of non-intubated techniques, it is unknown whether avoiding urinary catheters can enhance recovery. This study aimed to determine whether the tubeless urinary catheter protocol is feasible and beneficial for minimally invasive lung surgery. Patients were randomized to the control group, completely tubeless group, and partially tubeless group. A propensity score-matched (PSM) analysis was performed to balance the non-random baseline characteristics. Complications and postoperative recovery were compared. Regression analysis was performed to identify the independent predictors of complications. A nomogram for predicting the risk of non-automatic micturition was constructed and internally validated. One hundred fifty-nine patients were enrolled. The incidence rates of urinary irritation and urinary tract infection (UTI) were significantly lower in the tubeless groups (74.4 vs. 39.5%, < 0.001; 28.2 vs. 8.6%, = 0.001, respectively). The tubeless group had a higher proportion of 0-degree discomfort (81.5 vs. 30.8%, = 0.001) and shorter duration of postoperative hospital stay than the control group (4.59 vs. 5.53 days, < 0.001). No difference was observed in terms of urination retention and urinary incontinence between the tubeless group and the control group. After PSM, the advantages of the tubeless group still existed, and comparing to the partially tubeless group, the completely tubeless group was of even less UTI and more 0-degree discomfort (18.5 vs. 0.0%, = 0.019; 96.3 vs. 59.3%, = 0.002). The tubeless protocol was the only independent protective factor of urinary complications. A nomogram was constructed and showed good predictive ability. The tubeless catheterization protocol led to fewer complications, better compliance, and shorter hospital length of stay. The advantages were more significant with the completely tubeless protocol. The utility of our nomogram can assist clinicians in avoiding risks in performing the tubeless protocol.
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http://dx.doi.org/10.3389/fsurg.2020.584578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693547PMC
November 2020

Transcranial photoacoustic computed tomography based on a layered back-projection method.

Photoacoustics 2020 Dec 16;20:100213. Epub 2020 Oct 16.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.

A major challenge of transcranial human brain photoacoustic computed tomography (PACT) is correcting for the acoustic aberration induced by the skull. Here, we present a modified universal back-projection (UBP) method, termed layered UBP (L-UBP), that can de-aberrate the transcranial PA signals by accommodating the skull heterogeneity into conventional UBP. In L-UBP, the acoustic medium is divided into multiple layers: the acoustic coupling fluid layer between the skull and detectors, the skull layer, and the brain tissue layer, which are assigned different acoustic properties. The transmission coefficients and wave conversion are considered at the fluid-skull and skull-tissue interfaces. Simulations of transcranial PACT using L-UBP were conducted to validate the method. experiments with a newly developed three-dimensional PACT system with 1-MHz center frequency demonstrated that L-UBP can substantially improve the image quality compared to conventional UBP.
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http://dx.doi.org/10.1016/j.pacs.2020.100213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586244PMC
December 2020

Label-free imaging of lipid-rich biological tissues by mid-infrared photoacoustic microscopy.

J Biomed Opt 2020 10;25(10)

California Institute of Technology, Andrew and Peggy Cherng Department of Medical Engineering, Depar, United States.

Significance: Mid-infrared (IR) imaging based on the vibrational transition of biomolecules provides good chemical-specific contrast in label-free imaging of biology tissues, making it a popular tool in both biomedical studies and clinical applications. However, the current technology typically requires thin and dried or extremely flat samples, whose complicated processing limits this technology's broader translation.

Aim: To address this issue, we report mid-IR photoacoustic microscopy (PAM), which can readily work with fresh and thick tissue samples, even when they have rough surfaces.

Approach: We developed a transmission-mode mid-IR PAM system employing an optical parametric oscillation laser operating in the wavelength range from 2.5 to 12  μm. Due to its high sensitivity to optical absorption and the low ultrasonic attenuation of tissue, our PAM achieved greater probing depth than Fourier transform IR spectroscopy, thus enabling imaging fresh and thick tissue samples with rough surfaces.

Results: In our spectroscopy study, the CH2 symmetric stretching at 2850  cm  -  1 (3508 nm) was found to be an excellent source of endogenous contrast for lipids. At this wavenumber, we demonstrated label-free imaging of the lipid composition in fresh, manually cut, and unprocessed tissue sections of up to 3-mm thickness.

Conclusions: Our technology requires no time-consuming sample preparation procedure and has great potential in both fast clinical histological analysis and fundamental biological studies.
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http://dx.doi.org/10.1117/1.JBO.25.10.106506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720905PMC
October 2020

How we assess the perioperative anxiety of surgical patients with pulmonary nodules: the revision of state-trait anxiety inventory.

J Cardiothorac Surg 2020 Oct 28;15(1):324. Epub 2020 Oct 28.

Department of Thoracic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.

Purpose: The aim of the study was to develop a short form of State-Trait Anxiety Inventory (STAI) and calculate the norms for the assessment of anxiety in surgical patients in mainland China.

Methods: Patients who were scheduled to carry out pulmonary surgery in our department were included. The sinicized 40-item STAI Form-Y was used to assess the anxiety on the surgery eve. Then the coefficient of variation, coefficient of correlation, stepwise regression analysis, principal component analysis, and structural equation model were successively to filter the items. The reliability and validity of the revised STAI was estimated and the norms were computed.

Results: 445 intact replies were collected. A 13-item STAI with 6 items in state subscale and 7 items in trait subscale produced similar scores with the full version of STAI. The Cronbach alpha coefficients for the state and trait subscales were 0.924 and 0.936, respectively. The determinant coefficients were 0.781 and 0.822, respectively. Moreover, the norms of both state subscale and trait subscale are provided according to the age and gender.

Conclusions: The revised short form of STAI has good reliability and validity. It is likely to be more acceptable by reducing the fatigue effects, and is suitable for follow-up study on the assessment and intervention of perioperative anxiety of surgical patients with pulmonary nodules.
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http://dx.doi.org/10.1186/s13019-020-01338-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592361PMC
October 2020

Single-shot stereo-polarimetric compressed ultrafast photography for light-speed observation of high-dimensional optical transients with picosecond resolution.

Nat Commun 2020 10 16;11(1):5252. Epub 2020 Oct 16.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Mail Code 138-78, Pasadena, CA, 91125, USA.

Simultaneous and efficient ultrafast recording of multiple photon tags contributes to high-dimensional optical imaging and characterization in numerous fields. Existing high-dimensional optical imaging techniques that record space and polarization cannot detect the photon's time of arrival owing to the limited speeds of the state-of-the-art electronic sensors. Here, we overcome this long-standing limitation by implementing stereo-polarimetric compressed ultrafast photography (SP-CUP) to record light-speed high-dimensional events in a single exposure. Synergizing compressed sensing and streak imaging with stereoscopy and polarimetry, SP-CUP enables video-recording of five photon tags (x, y, z: space; t: time of arrival; and ψ: angle of linear polarization) at 100 billion frames per second with a picosecond temporal resolution. We applied SP-CUP to the spatiotemporal characterization of linear polarization dynamics in early-stage plasma emission from laser-induced breakdown. This system also allowed three-dimensional ultrafast imaging of the linear polarization properties of a single ultrashort laser pulse propagating in a scattering medium.
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http://dx.doi.org/10.1038/s41467-020-19065-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567836PMC
October 2020

Spatiotemporal strategies to identify aggressive biology in precancerous breast biopsies.

Wiley Interdiscip Rev Syst Biol Med 2020 Oct 1:e1506. Epub 2020 Oct 1.

Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California, USA.

Over 90% of breast cancer is cured; yet there remain highly aggressive breast cancers that develop rapidly and are extremely difficult to treat, much less prevent. Breast cancers that rapidly develop between breast image screening are called "interval cancers." The efforts of our team focus on identifying multiscale integrated strategies to identify biologically aggressive precancerous breast lesions. Our goal is to identify spatiotemporal changes that occur prior to development of interval breast cancers. To accomplish this requires integration of new technology. Our team has the ability to perform single cell in situ transcriptional profiling, noncontrast biological imaging, mathematical analysis, and nanoscale evaluation of receptor organization and signaling. These technological innovations allow us to start to identify multidimensional spatial and temporal relationships that drive the transition from biologically aggressive precancer to biologically aggressive interval breast cancer. This article is categorized under: Cancer > Computational Models Cancer > Molecular and Cellular Physiology Cancer > Genetics/Genomics/Epigenetics.
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http://dx.doi.org/10.1002/wsbm.1506DOI Listing
October 2020

EGFR in enterocytes & endothelium and HIF1α in enterocytes are dispensable for massive small bowel resection induced angiogenesis.

PLoS One 2020 15;15(9):e0236964. Epub 2020 Sep 15.

Division of Pediatric Surgery, Department of Surgery, St. Louis Children's Hospital, Washington University in St. Louis School of Medicine, St. Louis, MO, United States of America.

Background: Short bowel syndrome (SBS) results from significant loss of small intestinal length. In response to this loss, adaptation occurs, with Epidermal Growth Factor Receptor (EGFR) being a key driver. Besides enhanced enterocyte proliferation, we have revealed that adaptation is associated with angiogenesis. Further, we have found that small bowel resection (SBR) is associated with diminished oxygen delivery and elevated levels of hypoxia-inducible factor 1-alpha (HIF1α).

Methods: We ablated EGFR in the epithelium and endothelium as well as HIF1α in the epithelium, ostensibly the most hypoxic element. Using these mice, we determined the effects of these genetic manipulations on intestinal blood flow after SBR using photoacoustic microscopy (PAM), intestinal adaptation and angiogenic responses. Then, given that endothelial cells require a stromal support cell for efficient vascularization, we ablated EGFR expression in intestinal subepithelial myofibroblasts (ISEMFs) to determine its effects on angiogenesis in a microfluidic model of human small intestine.

Results: Despite immediate increased demand in oxygen extraction fraction measured by PAM in all mouse lines, were no differences in enterocyte and endothelial cell EGFR knockouts or enterocyte HIF1α knockouts by POD3. Submucosal capillary density was also unchanged by POD7 in all mouse lines. Additionally, EGFR silencing in ISEMFs did not impact vascular network development in a microfluidic device of human small intestine.

Conclusions: Overall, despite the importance of EGFR in facilitating intestinal adaptation after SBR, it had no impact on angiogenesis in three cell types-enterocytes, endothelial cells, and ISEMFs. Epithelial ablation of HIF1α also had no impact on angiogenesis in the setting of SBS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236964PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491746PMC
October 2020

Harnessing a multi-dimensional fibre laser using genetic wavefront shaping.

Light Sci Appl 2020 26;9:149. Epub 2020 Aug 26.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard Mail, Code 138-78, Pasadena, 91125 CA USA.

The multi-dimensional laser is a fascinating platform not only for the discovery and understanding of new higher-dimensional coherent lightwaves but also for the frontier study of the complex three-dimensional (3D) nonlinear dynamics and solitary waves widely involved in physics, chemistry, biology and materials science. Systemically controlling coherent lightwave oscillation in multi-dimensional lasers, however, is challenging and has largely been unexplored; yet, it is crucial for both designing 3D coherent light fields and unveiling any underlying nonlinear complexities. Here, for the first time, we genetically harness a multi-dimensional fibre laser using intracavity wavefront shaping technology such that versatile lasing characteristics can be manipulated. We demonstrate that the output power, mode profile, optical spectrum and mode-locking operation can be genetically optimized by appropriately designing the objective function of the genetic algorithm. It is anticipated that this genetic and systematic intracavity control technology for multi-dimensional lasers will be an important step for obtaining high-performance 3D lasing and presents many possibilities for exploring multi-dimensional nonlinear dynamics and solitary waves that may enable new applications.
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http://dx.doi.org/10.1038/s41377-020-00383-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450085PMC
August 2020

A Simple Method to Train the AI Diagnosis Model of Pulmonary Nodules.

Comput Math Methods Med 2020 1;2020:2812874. Epub 2020 Aug 1.

Department of Thoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, China.

Background: The differential diagnosis of subcentimetre lung nodules with a diameter of less than 1 cm has always been one of the problems of imaging doctors and thoracic surgeons. We plan to create a deep learning model for the diagnosis of pulmonary nodules in a simple method.

Methods: Image data and pathological diagnosis of patients come from the First Affiliated Hospital of Zhejiang University School of Medicine from October 1, 2016, to October 1, 2019. After data preprocessing and data augmentation, the training set is used to train the model. The test set is used to evaluate the trained model. At the same time, the clinician will also diagnose the test set.

Results: A total of 2,295 images of 496 lung nodules and their corresponding pathological diagnosis were selected as a training set and test set. After data augmentation, the number of training set images reached 12,510 images, including 6,648 malignant nodular images and 5,862 benign nodular images. The area under the - curve of the trained model is 0.836 in the classification of malignant and benign nodules. The area under the ROC curve of the trained model is 0.896 (95% CI: 78.96%~100.18%), which is higher than that of three doctors. However, the value is not less than 0.05.

Conclusion: With the help of an automatic machine learning system, clinicians can create a deep learning pulmonary nodule pathology classification model without the help of deep learning experts. The diagnostic efficiency of this model is not inferior to that of the clinician.
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http://dx.doi.org/10.1155/2020/2812874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416225PMC
August 2020

Multifocal photoacoustic microscopy using a single-element ultrasonic transducer through an ergodic relay.

Light Sci Appl 2020 31;9:135. Epub 2020 Jul 31.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 USA.

Optical-resolution photoacoustic microscopy (OR-PAM) has demonstrated high-spatial-resolution imaging of optical absorption in biological tissue. To date, most OR-PAM systems rely on mechanical scanning with confocally aligned optical excitation and ultrasonic detection, limiting the wide-field imaging speed of these systems. Although several multifocal OR-PA (MFOR-PA) systems have attempted to address this limitation, they are hindered by the complex design in a constrained physical space. Here, we present a two-dimensional (2D) MFOR-PAM system that utilizes a 2D microlens array and an acoustic ergodic relay. Using a single-element ultrasonic transducer, this system can detect PA signals generated from 400 optical foci in parallel and then raster scan the optical foci patterns to form an MFOR-PAM image. This system improves the imaging resolution of an acoustic ergodic relay system from 220 to 13 μm and enables 400-folds shorter scanning time than that of a conventional OR-PAM system at the same resolution and laser repetition rate. We demonstrated the imaging ability of the system with both in vitro and in vivo experiments.
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http://dx.doi.org/10.1038/s41377-020-00372-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393099PMC
July 2020

Intelligently optimized digital optical phase conjugation with particle swarm optimization.

Opt Lett 2020 Jan;45(2):431-434

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

Wavefront shaping (WFS) based on digital optical phase conjugation (DOPC) has gained major interest in focusing light through or inside scattering media. However, the quality of DOPC is greatly limited by imperfections of the system in a complicated and coupled way. In this Letter, we incorporate the concept of global optimization to solve this problem comprehensively for the first time, to the best of our knowledge. An automatic and intelligent optimization framework for DOPC techniques is proposed, leveraging the global optimization ability of particle swarm optimization (PSO). We demonstrate the general and powerful ability of the proposed approach in a series of DOPC-related experiments for focusing through and inside scattering media. This novel work can improve the OPC quality greatly and simplify the development of a high-performance DOPC system, which may open up a new avenue for the general scientific community to benefit from DOPC-based WFS in their potential applications.
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http://dx.doi.org/10.1364/ol.381930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398265PMC
January 2020

Spatiotemporal Antialiasing in Photoacoustic Computed Tomography.

IEEE Trans Med Imaging 2020 11 28;39(11):3535-3547. Epub 2020 Oct 28.

Photoacoustic computed tomography (PACT) based on a full-ring ultrasonic transducer array is widely used for small animal wholebody and human organ imaging, thanks to its high in-plane resolution and full-view fidelity. However, spatial aliasing in full-ring geometry PACT has not been studied in detail. If the spatial Nyquist criterion is not met, aliasing in spatial sampling causes artifacts in reconstructed images, even when the temporal Nyquist criterion has been satisfied. In this work, we clarified the source of spatial aliasing through spatiotemporal analysis. We demonstrated that the combination of spatial interpolation and temporal filtering can effectively mitigate artifacts caused by aliasing in either image reconstruction or spatial sampling, and we validated this method by both numerical simulations and in vivo experiments.
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http://dx.doi.org/10.1109/TMI.2020.2998509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654731PMC
November 2020

Time trend of mediastinal lymph node dissection in stage IA non-small cell lung cancer patient who undergo lobectomy: a retrospective study of surveillance, epidemiology, and end results (SEER) database.

J Cardiothorac Surg 2020 Aug 1;15(1):207. Epub 2020 Aug 1.

Department of thoracic surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China.

Background: Although lobectomy with mediastinal lymph node dissection (MLND) is the first option for early-stage non-small cell lung cancer (NSCLC) patients, the time trends of MLND in stage IA NSCLC patients who undergo a lobectomy are not clear still.

Methods: We included stage IA NSCLC patients who underwent lobectomy or lobectomy with MLND between 2003 and 2013 in the SEER database. The time trend of MLND was compared among patients who underwent a lobectomy.

Results: For stage T1a patients, the lobectomy group and lobectomy with MLND group had no differences in postoperative overall survival (OS) (P = 0.34) or lung-cancer specific survival (LCSS) (P = 0.18) between 2003 and 2013. For stage T1b patients, the OS (P = 0.01) and LCSS (P = 0.01) were different between the lobectomy group and the lobectomy with MLND group in the period from 2003 to 2009; however, only OS (P = 0.04), not LCSS (P = 0.14), was different between the lobectomy group and the lobectomy with MLND group between 2009 and 2013. For T1c patients, the OS (P = 0.01) and LCSS (P = 0.02) were different between the two groups between 2003 and 2009 but not between 2009 and 2013 (P = 0.60; P = 0.39). From the Cox regression analysis, we found that the factors affecting OS/LCSS in T1b and T1c patients were age, sex, year of diagnosis, histology, and grade, in which year of diagnosis was the obvious factor (HR = 0.79, CI = 0.71-0.87; HR = 0.73, CI = 0.64-0.84).

Conclusions: There was a time trend in prognosis differences between the lobectomy group and lobectomy with MLND group for T1b and T1c stage NSCLC patients.
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http://dx.doi.org/10.1186/s13019-020-01215-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395351PMC
August 2020

Liriopesides B induces apoptosis and cell cycle arrest in human non‑small cell lung cancer cells.

Int J Mol Med 2020 Sep 16;46(3):1039-1050. Epub 2020 Jun 16.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 350002, P.R. China.

Although significant progress has been made in the treatment of lung cancer, it remains the leading cause of cancer‑associated mortality. Liriopesides B (LPB) is a natural product isolated from the tuber of Liriope platyphylla, whose effective substances have exhibited antitumor activity in several types of cancer. However, the functions of LPB in non‑small cell lung cancer (NSCLC) require further investigation. Therefore, the present study aimed to investigate whether LPB influences the pathogenic effects of NSCLC. In the present study, it was demonstrated that LPB reduced proliferation, and induced apoptosis and cell cycle arrest in non‑small cell lung cancer cells. CCK‑8 and colony formation assays demonstrated that LPB decreased cell viability and proliferation of H460 and H1975 cells in a dose‑dependent manner. Flow cytometry revealed that LPB significantly induced apoptosis of NSCLC cells, along with changes in the expression of apoptosis‑associated proteins, including an increase in Bax, caspase‑3, and caspase‑8 expression, and a decrease in Bcl‑2 and Bcl‑xl expression. LPB inhibited the progression of the cell cycle from the G1 to the S phase. Furthermore, autophagy was increased in cells treated with LPB. Finally, the expression of programmed death‑ligand 1 was significantly decreased by LPB. In conclusion, the results of the present study highlight a potential novel strategy for the clinical treatment of NSCLC.
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http://dx.doi.org/10.3892/ijmm.2020.4645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387084PMC
September 2020

Photoacoustic topography through an ergodic relay for functional imaging and biometric application in vivo.

J Biomed Opt 2020 07;25(7):1-8

California Institute of Technology, Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Depa, United States.

Significance: Photoacoustic (PA) tomography has demonstrated versatile biomedical applications. However, an array-based PA computed tomography (PACT) system is complex and expensive, whereas a single-element detector-based scanning PA system is too slow to detect some fast biological dynamics in vivo. New PA imaging methods are sought after.

Aim: To overcome these limitations, we developed photoacoustic topography through an ergodic relay (PATER), a novel high-speed imaging system with a single-element detector.

Approach: PATER images widefield PA signals encoded by the acoustic ergodic relay with a single-laser shot.

Results: We applied PATER in vivo to monitor changes in oxygen saturation in a mouse brain and also to demonstrate high-speed matching of vascular patterns for biometric authentication.

Conclusions: PATER has achieved a high-speed temporal resolution over a large field of view. Our results suggest that PATER is a promising and economical alternative to PACT for fast imaging.
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http://dx.doi.org/10.1117/1.JBO.25.7.070501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347463PMC
July 2020

A microrobotic system guided by photoacoustic computed tomography for targeted navigation in intestines .

Sci Robot 2019 Jul 24;4(32). Epub 2019 Jul 24.

Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, USA.

Recently, tremendous progress in synthetic micro/nanomotors in diverse environment has been made for potential biomedical applications. However, existing micro/nanomotor platforms are inefficient for deep tissue imaging and motion control . Here, we present a photoacoustic computed tomography (PACT) guided investigation of micromotors in intestines . The micromotors enveloped in microcapsules are stable in the stomach and exhibit efficient propulsion in various biofluids once released. The migration of micromotor capsules toward the targeted regions in intestines has been visualized by PACT in real time . Near-infrared light irradiation induces disintegration of the capsules to release the cargo-loaded micromotors. The intensive propulsion of the micromotors effectively prolongs the retention in intestines. The integration of the newly developed microrobotic system and PACT enables deep imaging and precise control of the micromotors and promises practical biomedical applications, such as drug delivery.
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http://dx.doi.org/10.1126/scirobotics.aax0613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337196PMC
July 2019