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Browsing by Author "Cheng, Ji-Xin"
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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 Assessment of white matter loss using bond-selective photoacoustic imaging in a rat model of contusive spinal cord injury(Mary Ann Liebert, 2014-12-15) Wu, Wei; Wang, Pu; Cheng, Ji-Xin; Xu, Xiao-Ming; Department of Neurological Surgery, IU School of MedicineWhite matter (WM) loss is a critical event after spinal cord injury (SCI). Conventionally, such loss has been measured with histological and histochemical approaches, although the procedures are complex and may cause artifact. Recently, coherent Raman microscopy has been proven to be an emerging technology to study de- and remyelination of the injured spinal cord; however, limited penetration depth and small imaging field prevent it from comprehensive assessments of large areas of damaged tissues. Here, we report the use of bond-selective photoacoustic (PA) imaging with 1730-nm excitation, where the first overtone vibration of CH2 bond is located, to assess WM loss after a contusive SCI in adult rats. By employing the first overtone vibration of CH2 bond as the contrast, the mapping of the WM in an intact spinal cord was achieved in a label-free three-dimensional manner, and the physiological change of the spinal cord before and after injury was observed. Moreover, the recovery of the spinal cord from contusive injury with the treatment of a neuroprotective nanomedicine ferulic-acid-conjugated glycol chitosan (FA-GC) was also observed. Our study suggests that bond-selective PA imaging is a valuable tool to assess the progression of WM pathology after SCI as well as neuroprotective therapeutics in a label-free manner.Item Biaxial deformation of collagen and elastin fibers in coronary adventitia(American Physiological Society (APS), 2013-12-01) Chen, Huan; Slipchenko, Mikhail N.; Liu, Yi; Zhao, Xuefeng; Cheng, Ji-Xin; Lanir, Yoram; Kassab, Ghassan S.; Department of Biomedical Engineering, Purdue School of Engineering and Technology, IUPUIThe microstructural deformation-mechanical loading relation of the blood vessel wall is essential for understanding the overall mechanical behavior of vascular tissue in health and disease. We employed simultaneous mechanical loading-imaging to quantify in situ deformation of individual collagen and elastin fibers on unstained fresh porcine coronary adventitia under a combination of vessel inflation and axial extension loading. Specifically, the specimens were imaged under biaxial loads to study microscopic deformation-loading behavior of fibers in conjunction with morphometric measurements at the zero-stress state. Collagen fibers largely orientate in the longitudinal direction, while elastin fibers have major orientation parallel to collagen, but with additional orientation angles in each sublayer of the adventitia. With an increase of biaxial load, collagen fibers were uniformly stretched to the loading direction, while elastin fibers gradually formed a network in sublayers, which strongly depended on the initial arrangement. The waviness of collagen decreased more rapidly at a circumferential stretch ratio of λθ = 1.0 than at λθ = 1.5, while most collagen became straightened at λθ = 1.8. These microscopic deformations imply that the longitudinally stiffer adventitia is a direct result of initial fiber alignment, and the overall mechanical behavior of the tissue is highly dependent on the corresponding microscopic deformation of fibers. The microstructural deformation-loading relation will serve as a foundation for micromechanical models of the vessel wall.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 Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness(Elsevier, 2014-03-04) Yue, Shuhua; Li, Junjie; Lee, Seung-Young; Lee, Hyeon Jeong; Shao, Tian; Song, Bing; Cheng, Liang; Masterson, Timothy A.; Liu, Xiaoqi; Ratliff, Timothy L.; Cheng, Ji-Xin; Department of Pathology & Laboratory Medicine, IU School of MedicineAltered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.Item Comparative Quantification of Arterial Lipid by Intravascular Photoacoustic-Ultrasound Imaging and Near-Infrared Spectroscopy-Intravascular Ultrasound(Springer, 2018-11-28) Kole, Ayeeshik; Cao, Yingchun; Hui, Jie; Bolad, Islam A.; Alloosh, Mouhamad; Cheng, Ji-Xin; Sturek, Michael; Cellular and Integrative Physiology, School of MedicineIntravascular photoacoustic-ultrasound (IVPA-US) imaging and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) are two hybrid modalities that detect arterial lipid, with comparison necessary to understand the relative advantages of each. We performed in vivo and ex vivo IVPA-US imaging of the iliac arteries of Ossabaw swine with metabolic syndrome (MetS) and lean swine to investigate sensitivity for early-stage atherosclerosis. We repeated imaging ex vivo with NIRS-IVUS for comparison to IVPA-US and histology. Both modalities showed significantly greater lipid in MetS vs. lean swine, but only IVPA-US localized the lipid as perivascular. To investigate late-stage atherosclerosis, we performed ex vivo IVPA-US imaging of a human coronary artery with comparison to NIRS-IVUS and histology. Two advanced fibroatheromas were identified, with agreement between IVPA-measured lipid area and NIRS-derived lipid content. As confirmed histologically, IVPA-US has sensitivity to detect lipid content similar to NIRS-IVUS and provides additional depth resolution, enabling quantification and localization of lipid cores within plaques.Item Cylindrical illumination with angular coupling for whole-prostate photoacoustic tomography(Optical Society of America, 2019-02-22) Bungart, Brittani; Cao, Yingchun; Yang-Tran, Tiffany; Gorsky, Sean; Lan, Lu; Roblyer, Darren; Koch, Michael O.; Cheng, Liang; Masterson, Timothy; Cheng, Ji-Xin; Department of Medicine, IU School of MedicineCurrent diagnosis of prostate cancer relies on histological analysis of tissue samples acquired by biopsy, which could benefit from real-time identification of suspicious lesions. Photoacoustic tomography has the potential to provide real-time targets for prostate biopsy guidance with chemical selectivity, but light delivered from the rectal cavity has been unable to penetrate to the anterior prostate. To overcome this barrier, a urethral device with cylindrical illumination is developed for whole-prostate imaging, and its performance as a function of angular light coupling is evaluated with a prostate-mimicking phantom.Item Fast assessment of lipid content in arteries in vivo by intravascular photoacoustic tomography(Nature Publishing Group, 2018-02-05) Cao, Yingchun; Kole, Ayeeshik; Hui, Jie; Zhang, Yi; Mai, Jieying; Alloosh, Mouhamad; Sturek, Michael; Cheng, Ji-Xin; Cellular and Integrative Physiology, School of MedicineIntravascular photoacoustic tomography is an emerging technology for mapping lipid deposition within an arterial wall for the investigation of the vulnerability of atherosclerotic plaques to rupture. By converting localized laser absorption in lipid-rich biological tissue into ultrasonic waves through thermoelastic expansion, intravascular photoacoustic tomography is uniquely capable of imaging the entire arterial wall with chemical selectivity and depth resolution. However, technical challenges, including an imaging catheter with sufficient sensitivity and depth and a functional sheath material without significant signal attenuation and artifact generation for both photoacoustics and ultrasound, have prevented in vivo application of intravascular photoacoustic imaging for clinical translation. Here, we present a highly sensitive quasi-collinear dual-mode photoacoustic/ultrasound catheter with elaborately selected sheath material, and demonstrated the performance of our intravascular photoacoustic tomography system by in vivo imaging of lipid distribution in rabbit aortas under clinically relevant conditions at imaging speeds up to 16 frames per second. Ex vivo evaluation of fresh human coronary arteries further confirmed the performance of our imaging system for accurate lipid localization and quantification of the entire arterial wall, indicating its clinical significance and translational capability.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 Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis(American Association for Cancer Research, 2021-01-15) Wang, Yinu; Zhao, Guangyuan; Condello, Salvatore; Huang, Hao; Cardenas, Horacio; Tanner, Edward J.; Wei, JianJun; Ji, Yanrong; Li, Junjie; Tan, Yuying; Davuluri, Ramana V.; Peter, Marcus E.; Cheng, Ji-Xin; Matei, Daniela; Obstetrics and Gynecology, School of MedicineDefining traits of platinum-tolerant cancer cells could expose new treatment vulnerabilities. Here, new markers associated with platinum-tolerant cells and tumors were identified using in vitro and in vivo ovarian cancer (OC) models treated repetitively with carboplatin and validated in human specimens. Platinum-tolerant cells and tumors were enriched in ALDH(+) cells, formed more spheroids, and expressed increased levels of stemness-related transcription factors compared to parental cells. Additionally, platinum-tolerant cells and tumors exhibited expression of the Wnt receptor Frizzled 7 (FZD7). Knockdown of FZD7 improved sensitivity to platinum, decreased spheroid formation, and delayed tumor initiation. The molecular signature distinguishing FZD7(+) from FZD7(−) cells included epithelial-to-mesenchymal (EMT), stemness, and oxidative phosphorylation-enriched gene sets. Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7(+) platinum-tolerant OC cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors. FZD7, Tp63, and glutathione metabolism gene sets were strongly correlated in the OC Tumor Cancer Genome Atlas (TCGA) database and in residual human OC specimens after chemotherapy. These results support the existence of a platinum-tolerant cell population with partial cancer stem cell features, characterized by FZD7 expression and dependent on FZD7-β-catenin-Tp63-GPX4 pathway for survival. The findings reveal a novel therapeutic vulnerability of platinum-tolerant cancer cells and provide new insight into a potential “persister cancer cell” phenotype.
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