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Browsing by Author "Li, Rui"
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Item Assessing breast tumor margin by multispectral photoacoustic tomography(Optical Society of America, 2015-03-12) Li, Rui; Wang, Pu; Lan, Lu; Lloyd Jr., Frank P.; Goergen, Craig J.; Chen, Shaoxiong; Cheng, Ji-Xin; Department of Pathology and Laboratory Medicine, IU School of MedicineAn unmet need exists in high-speed and highly-sensitive intraoperative assessment of breast cancer margin during conservation surgical procedures. Here, we demonstrate a multispectral photoacoustic tomography system for breast tumor margin assessment using fat and hemoglobin as contrasts. This system provides ~3 mm tissue depth and ~125 μm axial resolution. The results agreed with the histological findings. A high sensitivity in margin assessment was accomplished, which opens a compelling way to intraoperative margin assessment.Item Automated monitoring of early neurobehavioral changes in mice following traumatic brain injury(Medknow Publications, 2016-02) Qu, Wenrui; Liu, Nai-Kui; Xie, Xin-Min Simon; Li, Rui; Xu, Xiao-Ming; Department of Neurological Surgery, IU School of MedicineTraumatic brain injury often causes a variety of behavioral and emotional impairments that can develop into chronic disorders. Therefore, there is a need to shift towards identifying early symptoms that can aid in the prediction of traumatic brain injury outcomes and behavioral endpoints in patients with traumatic brain injury after early interventions. In this study, we used the SmartCage system, an automated quantitative approach to assess behavior alterations in mice during an early phase of traumatic brain injury in their home cages. Female C57BL/6 adult mice were subjected to moderate controlled cortical impact (CCI) injury. The mice then received a battery of behavioral assessments including neurological score, locomotor activity, sleep/wake states, and anxiety-like behaviors on days 1, 2, and 7 after CCI. Histological analysis was performed on day 7 after the last assessment. Spontaneous activities on days 1 and 2 after injury were significantly decreased in the CCI group. The average percentage of sleep time spent in both dark and light cycles were significantly higher in the CCI group than in the sham group. For anxiety-like behaviors, the time spent in a light compartment and the number of transitions between the dark/light compartments were all significantly reduced in the CCI group than in the sham group. In addition, the mice suffering from CCI exhibited a preference of staying in the dark compartment of a dark/light cage. The CCI mice showed reduced neurological score and histological abnormalities, which are well correlated to the automated behavioral assessments. Our findings demonstrate that the automated SmartCage system provides sensitive and objective measures for early behavior changes in mice following traumatic brain injury.Item Bond-selective photoacoustic imaging by converting molecular vibration into acoustic waves(Elsevier, 2016-03) Hui, Jie; Li, Rui; Phillips, Evan H.; Goergen, Craig J.; Sturek, Michael; Cheng, Ji-Xin; Department of Cellular & Integrative Physiology, IU School of MedicineThe quantized vibration of chemical bonds provides a way of detecting specific molecules in a complex tissue environment. Unlike pure optical methods, for which imaging depth is limited to a few hundred micrometers by significant optical scattering, photoacoustic detection of vibrational absorption breaks through the optical diffusion limit by taking advantage of diffused photons and weak acoustic scattering. Key features of this method include both high scalability of imaging depth from a few millimeters to a few centimeters and chemical bond selectivity as a novel contrast mechanism for photoacoustic imaging. Its biomedical applications spans detection of white matter loss and regeneration, assessment of breast tumor margins, and diagnosis of vulnerable atherosclerotic plaques. This review provides an overview of the recent advances made in vibration-based photoacoustic imaging and various biomedical applications enabled by this new technology.Item Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury(Wolters Kluwer, 2025) Qu, Wenrui; Wu, Xiangbing; Wu, Wei; Wang, Ying; Sun, Yan; Deng, Lingxiao; Walker, Melissa; Chen, Chen; Dai, Heqiao; Han, Qi; Ding, Ying; Xia, Yongzhi; Smith, George; Li, Rui; Liu, Nai-Kui; Xu, Xiao-Ming; Neurological Surgery, School of MedicineSchwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.Item Disrupting nNOS–PSD95 Interaction Improves Neurological and Cognitive Recoveries after Traumatic Brain Injury(Oxford University Press, 2020-06) Qu, Wenrui; Liu, Nai-Kui; Wu, Xiangbing; Wang, Ying; Xia, Yongzhi; Sun, Yan; Lai, Yvonne; Li, Rui; Shekhar, Anantha; Xu, Xiao-Ming; Psychiatry, School of MedicineExcessive activation of N-methyl-D-aspartate receptors (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation plays a crucial role in the pathogenesis of traumatic brain injury (TBI). However, directly inhibiting NMDARs or nNOS produces adverse side effects because they play key physiological roles in the normal brain. Since interaction of nNOS–PSD95 is a key step in NMDAR-mediated excitotoxicity, we investigated whether disrupting nNOS–PSD95 interaction with ZL006, an inhibitor of nNOS–PSD95 interaction, attenuates NMDAR-mediated excitotoxicity. In cortical neuronal cultures, ZL006 treatment significantly reduced glutamate-induced neuronal death. In a mouse model of controlled cortical impact (CCI), administration of ZL006 (10 mg/kg, i.p.) at 30 min postinjury significantly inhibited nNOS–PSD95 interaction, reduced TUNEL- and phospho-p38-positive neurons in the motor cortex. ZL006 treatment also significantly reduced CCI-induced cortical expression of apoptotic markers active caspase-3, PARP-1, ratio of Bcl-2/Bax, and phosphorylated p38 MAPK (p-p38). Functionally, ZL006 treatment significantly improved neuroscores and sensorimotor performance, reduced somatosensory and motor deficits, reversed CCI-induced memory deficits, and attenuated cognitive impairment. Histologically, ZL006 treatment significantly reduced the brain lesion volume. These findings collectively suggest that blocking nNOS–PSD95 interaction represents an attractive strategy for ameliorating consequences of TBI and that its action is mediated via inhibiting neuronal apoptosis and p38 MAPK signaling.Item A fiber optoacoustic guide with augmented reality for precision breast-conserving surgery(Springer Nature, 2018-05-18) Lan, Lu; Xia, Yan; Li, Rui; Liu, Kaiming; Mai, Jieying; Medley, Jennifer Anne; Obeng-Gyasi, Samilia; Han, Linda K.; Wang, Pu; Cheng, Ji-Xin; Radiology and Imaging Sciences, School of MedicineLumpectomy, also called breast-conserving surgery, has become the standard surgical treatment for early-stage breast cancer. However, accurately locating the tumor during a lumpectomy, especially when the lesion is small and nonpalpable, is a challenge. Such difficulty can lead to either incomplete tumor removal or prolonged surgical time, which result in high re-operation rates (~25%) and increased surgical costs. Here, we report a fiber optoacoustic guide (FOG) with augmented reality (AR) for sub-millimeter tumor localization and intuitive surgical guidance with minimal interference. The FOG is preoperatively implanted in the tumor. Under external pulsed light excitation, the FOG omnidirectionally broadcasts acoustic waves through the optoacoustic effect by a specially designed nano-composite layer at its tip. By capturing the acoustic wave, three ultrasound sensors on the breast skin triangulate the FOG tip's position with 0.25-mm accuracy. An AR system with a tablet measures the coordinates of the ultrasound sensors and transforms the FOG tip's position into visual feedback with <1-mm accuracy, thus aiding surgeons in directly visualizing the tumor location and performing fast and accurate tumor removal. We further show the use of a head-mounted display to visualize the same information in the surgeons' first-person view and achieve hands-free guidance. Towards clinical application, a surgeon successfully deployed the FOG to excise a "pseudo tumor" in a female human cadaver. With the high-accuracy tumor localization by FOG and the intuitive surgical guidance by AR, the surgeon performed accurate and fast tumor removal, which will significantly reduce re-operation rates and shorten the surgery time.Item Impact of time-varying confounders on the association between early-life allergy sensitization and the risk of current asthma: A post hoc analysis of a birth cohort(Wiley, 2022) Owora, Arthur H.; Li, Rui; Tepper, Robert S.; Ramsey, Clare D.; Chan-Yeung, Moira; Watson, Wade T. A.; Becker, Allan B.; Epidemiology, School of Public HealthItem Interaction between Schwann cells and other cells during repair of peripheral nerve injury(Wolters Kluwer, 2021-01) Qu, Wen-Rui; Zhu, Zhe; Liu, Jun; Song, De-Biao; Tian, Heng; Chen, Bing-Peng; Li, Rui; Deng, Ling-Xiao; Neurological Surgery, School of MedicinePeripheral nerve injury (PNI) is common and, unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury. Peripheral myelinating glia, Schwann cells (SCs), interact with various cells in and around the injury site and are important for debris elimination, repair, and nerve regeneration. Following PNI, Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages. Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair. The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve. In particular, SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers. This mobility increases SC interactions with other cells in the nerve and the exogenous environment, which influence SC behavior post-injury. Following PNI, SCs directly and indirectly interact with other SCs, fibroblasts, and macrophages. In addition, the inter- and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve. This review provides a basic assessment of SC function post-PNI, as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and, ultimately, repair of the injured nerve.Item Nomogram for prediction of portal vein system thrombosis after splenectomy for hypersplenism in patients with Wilson disease(APM, 2022-12-28) Yao, Yu; Zhang, Juan; Jiang, Huaizhou; Li, Rui; Xie, Daojun; Jiang, Feng; Zhang, Wanqiu; Ma, Min; Biology, School of ScienceBackground: The occurrence of portal vein system thrombosis (PVST) after splenectomy in patients with Wilson disease (WD) can lead to serious complications. The early identification of high-risk patients can help improve patient prognosis. This study aimed to establish and validate a personalized nomogram for assessing the risk of PVST after splenectomy in patients with WD and hypersplenism. Methods: We retrospectively collected the data from 81 patients with WD and hypersplenism who underwent splenectomy. Based on whether PVST occurred within a month after the operation, they were divided into the PVST group and the non-PVST group. The clinical data of the 2 groups were compared, and univariate analysis was used to select the statistically significant features and incorporated into the least absolute shrinkage and selection operator (LASSO) regression model for optimization. Multivariate logistic regression analysis was used to determine the independent risk factors for PVST after splenectomy, which were then applied to establish a personalized nomogram. We calculated the concordance (C)-index and drew the receiver operating characteristic (ROC) curve, the model calibration curve, and the clinical decision analysis (DCA) curve to evaluate the accuracy, calibration, and clinical applicability of the model, respectively. We used bootstrapping for internal validation of the model. Results: Univariate analysis showed that the differences in preoperative portal vein diameter and velocity of portal blood flow, postoperative mean platelet volume (MPV), mean platelet distribution width (PDW), D-dimer, prothrombin time (PT), and the increase of platelet count (PLT) were of statistical significance (P<0.05). According to the results of the LASSO and multivariate logistic regression analyses, a model including preoperative portal vein diameter, preoperative portal blood flow velocity, postoperative D-dimer, and the increase of PLT was established to predict the risk of PVST after splenectomy. The model showed good accuracy with a C-index of 0.838 (95% CI: 0.750–0.926) and had a well-fitted calibration curve. Furthermore, internal validation showed it achieved a moderate C-index of 0.805. The DCA curve indicated that the model has clinical applicability when patients are treated at thresholds of 2–100%. Conclusions: Establishing a predictive model for the risk of PVST in patients with WD and hypersplenism after splenectomy can help clinicians identify patients at high risk of PVST who require intervention measures.Item Photoacoustic tomography of intact human prostates and vascular texture analysis identify prostate cancer biopsy targets(Elsevier, 2018-08-03) Bungart, Brittani L.; Lan, Lu; Wang, Pu; Li, Rui; Koch, Michael O.; Cheng, Liang; Masterson, Timothy A.; Dundar, Murat; Cheng, Jin-Xin; Urology, School of MedicineProstate cancer is poorly visualized on ultrasonography (US) so that current biopsy requires either a templated technique or guidance after fusion of US with magnetic resonance imaging. Here we determined the ability for photoacoustic tomography (PAT) and US followed by texture-based image processing to identify prostate biopsy targets. K-means clustering feature learning and testing was performed on separate datasets comprised of 1064 and 1197 nm PAT and US images of intact, ex vivo human prostates. 1197 nm PAT was found to not contribute to the feature learning, and thus, only 1064 nm PAT and US images were used for final feature testing. Biopsy targets, determined by the tumor-assigned pixels' center of mass, located 100% of the primary lesions and 67% of the secondary lesions. In conclusion, 1064 nm PAT and US texture-based feature analysis provided successful prostate biopsy targets.