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31 result(s) for "Beop-Min Kim"
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Macrophages‐Triggered Sequential Remodeling of Endothelium‐Interstitial Matrix to Form Pre‐Metastatic Niche in Microfluidic Tumor Microenvironment
The primed microenvironment of future metastatic sites, called the pre‐metastatic niche, is a prerequisite for overt metastasis. However, a mechanistic understanding of the contributions of recruited cells to the niche is hindered by complex in vivo systems. Herein, a microfluidic platform that incorporates endothelial cells and extracellular matrix (ECM) scaffolds is developed, and the distinct role of recruited monocytes and macrophages in establishing pre‐metastatic niches is delineated. It is observed that monocyte‐derived matrix metalloproteinase 9 facilitates cancer cell extravasation through destruction of endothelial tight junctions. Furthermore, subsequent cancer cell invasiveness is significantly enhanced. Close examination of ECM structures reveals that cancer cells move within characteristic “microtracks” generated by macrophages, suggesting that macrophages could serve as a compensatory mechanism for the reduced migratory capacity of cancer cells. Thus, the first evidence of monocyte/macrophage‐induced remodeling is shown, and these findings will open up new horizons for improving characterization of the pre‐metastatic niche and corresponding immunotherapies. Vascular leakage and stroma remodeling by stromal cells are known as initiators for pre‐metastatic niches. In this study, based on the 3D reconstitution of multicellular pre‐metastatic niches, macrophage‐triggered remodeling of endothelium‐interstitial matrix continuum facilitating cancer cell invasion is investigated. The sequential remodeling could be a novel compensatory mechanism for cancer cells to sustain invasiveness within the niches.
Resting-state hemodynamic changes and effects on upper limb function after multi-channel transcranial direct current stimulation to the ipsilesional primary motor cortex and anterior intraparietal sulcus in stroke patients: an fNIRS pilot study
Background Stroke results in substantial long-term disability, necessitating effective recovery interventions. This study explored the effects of multi-channel transcranial direct current stimulation (tDCS) on hemodynamic responses and upper limb motor function in stroke patients, targeting the ipsilesional primary motor cortex (M1) and anterior intraparietal sulcus (aIPS). Methods A double-blind, randomized, sham-controlled trial was conducted with 24 stroke patients (18 men; mean age, 57.3×14.2 years), who underwent 10 sessions of real or sham multi-channel tDCS combined with upper limb exercises. Functional near-infrared spectroscopy (fNIRS) measured resting-state cerebral hemodynamic responses for 5 min before and after each session. Motor function was evaluated using the Fugl–Meyer assessment for upper extremity (FMA-UE), box and block test (BBT), and other motor function tests before and after the interventions. Results The real multi-channel tDCS group exhibited increases in regional accumulation of oxyhemoglobin (HbO Acc ) and stronger seeded connectivity networks within the motor cortex poststimulation. In contrast, the sham group exhibited disassociation from these areas. The group × time interaction was significant for the Box and Block Test (BBT), indicating greater improvements in gross manual dexterity in the real-tDCS group compared to the sham group. While poststimulation changes in HbOAcc were examined in relation to FMA-UE scores, no strong linear relationship was observed in the real-tDCS group. Conclusions Multi-channel tDCS targeting the ipsilesional M1 and aIPS, combined with upper limb exercises, showed potential effects on cerebral hemodynamics and motor function in stroke patients. These findings suggest that multi-channel tDCS may have a role in motor rehabilitation, but further research is needed to validate its efficacy and clinical applicability. ClinicalTrials.gov This study was registered at ClinicalTrials.gov (NCT05275114).
The effect of pupil transmittance on axial resolution of reflection phase microscopy
A reflection phase microscope (RPM) can be equipped with the capability of depth selection by employing a gating mechanism. However, it is difficult to achieve an axial resolution close to the diffraction limit in real implementation. Here, we systematically investigated the uneven interference contrast produced by pupil transmittance of the objective lens and found that it was the main cause of the practical limit that prevents the axial resolution from reaching its diffraction limit. Then we modulated the power of illumination light to obtain a uniform interference contrast over the entire pupil. Consequently, we could achieve an axial resolution fairly close to the diffraction limit set by the experimental conditions.
Simultaneous Visualization of Lung Tumor and Intersegmental Plane during Pulmonary Segmentectomy by Intravenous Injection of Indocyanine Green
Segmentectomy is a targeted surgical approach tailored for patients with compromised health and early-stage lung cancer. The key to successful segmentectomy lies in precisely identifying the tumor and intersegmental planes to ensure adequate resection margins. In this study, we aimed to enhance this process by simultaneously visualizing the tumor and intersegmental planes through the intravenous injection of indocyanine green (ICG) at different time points and doses. Lung tumors were detected by intravenous injection of ICG at a dose of 2 mg/kg 12 h before surgery in a rabbit model. Following the dissection of the pulmonary artery, vein, and bronchi of the target segment, 0.6 mg/kg of ICG was injected intravenously to detect the intersegmental plan. Fluorescent images of the lung tumors and segments were acquired, and the fluorescent signal was quantified using the signal-to-background ratio (SBR). Finally, a pilot study of this method was conducted in three patients with lung cancer. In a preclinical study, the SBR of the tumor (4.4 ± 0.1) and nontargeted segments (10.5 ± 0.8) were significantly higher than that of the targeted segment (1.6 ± 0.2) (targeted segment vs. nontarget segment, p < 0.0001; target segment vs. tumor, p < 0.01). Consistent with preclinical results, lung tumors and the intersegmental plane were successfully detected in patients with lung cancer. Consequently, adequate resection margins were identified during the surgery, and segmentectomy was successfully performed in patients with lung cancer. This study is the first to use intravenous ICG injections at different time points and doses to simultaneously detect lung cancer and intersegmental planes, thereby achieving segmentectomy for lung cancer.
Optimization of Indocyanine Green for Intraoperative Fluorescent Image-Guided Localization of Lung Cancer; Analysis Based on Solid Component of Lung Nodule
ICG fluorescence imaging has been used to detect lung cancer; however, there is no consensus regarding the optimization of the indocyanine green (ICG) injection method. The aim of this study was to determine the optimal dose and timing of ICG for lung cancer detection using animal models and to evaluate the feasibility of ICG fluorescence in lung cancer patients. In a preclinical study, twenty C57BL/6 mice with footpad cancer and thirty-three rabbits with VX2 lung cancer were used. These animals received an intravenous injection of ICG at 0.5, 1, 2, or 5 mg/kg, and the cancers were detected using a fluorescent imaging system after 3, 6, 12, and 24 h. In a clinical study, fifty-one patients diagnosed with lung cancer and scheduled to undergo surgery were included. Fluorescent images of lung cancer were obtained, and the fluorescent signal was quantified. Based on a preclinical study, the optimal injection method for lung cancer detection was 2 mg/kg ICG 12 h before surgery. Among the 51 patients, ICG successfully detected 37 of 39 cases with a consolidation-to-tumor (C/T) ratio of >50% (TNR: 3.3 ± 1.2), while it failed in 12 cases with a C/T ratio ≤ 50% and 2 cases with anthracosis. ICG injection at 2 mg/kg, 12 h before surgery was optimal for lung cancer detection. Lung cancers with the C/T ratio > 50% were successfully detected using ICG with a detection rate of 95%, but not with the C/T ratio ≤ 50%. Therefore, further research is needed to develop fluorescent agents targeting lung cancer.
Cerebral Perfusion Monitoring Using Near-Infrared Spectroscopy During Head-Up Tilt Table Test in Patients With Orthostatic Intolerance
The head-up tilt table test (HUT) is one of the primary clinical examinations for evaluating orthostatic intolerance (OI). HUT can be divided into three phases: dynamic tilt phase (supine to tilt up), static tilt phase (remain tilted at 70°), and post tilt phase (tilt down back to supine position). Commonly, blood pressure (BP) and heart rate (HR) are monitored to observe for OI symptoms, but are indirect measurements of cerebral perfusion and can lead to inaccurate HUT evaluation. In this study, we implemented a 108-channel near-infrared spectroscopy (NIRS) probe to characterize HUT performance by monitoring cerebral hemodynamic changes for healthy controls (HCs), OI patients with normal HUT results, and OI patients with positive HUT results: vasovagal syncope (VS), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), and orthostatic hypertension (OHT). By the end of the static tilt phase, OI patients typically did not show a complete recovery back to baseline cerebral oxygenation and total blood volume compared to HCs. We characterized the return to cerebral homeostasis by polynomial fitting total blood volume changes and determining the inflection point. The OI patients with normal HUT results, VS, OH, or OHT showed a delay in the return to cerebral homeostasis compared to the HC group during HUT.
Laser–tissue interaction simulation considering skin-specific data to predict photothermal damage lesions during laser irradiation
Abstract This study aimed to develop a simulation model that accounts for skin-specific properties in order to predict photothermal damage during skin laser treatment. To construct a computational model, surface geometry information was obtained from an optical coherence tomography image, and the absorption coefficient of the skin was determined through spectrophotometry. The distribution of the internal light dose inside the skin medium was calculated using the light propagation model based on the Monte Carlo method. The photothermal response due to the absorption of laser light was modeled by a finite difference time domain model to solve the bio-heat transfer equation. The predicted depth and area of the damaged lesions from the simulation model were compared to those measured in ex vivo porcine skin. The present simulation model gave acceptable predictions with differences of approximately ∼10% in both depth and area. Graphical Abstract Graphical Abstract
Identification of Metastatic Lymph Nodes Using Indocyanine Green Fluorescence Imaging
Indocyanine green (ICG) has been used to detect several types of tumors; however, its ability to detect metastatic lymph nodes (LNs) remains unclear. Our goal was to determine the feasibility of ICG in detecting metastatic LNs. We established a mouse model and evaluated the potential of ICG. The feasibility of detecting metastatic LNs was also evaluated in patients with lung or esophageal cancer, detected with computed tomography (CT) or positron-emission tomography (PET)/CT, and scheduled to undergo surgical resection. Tumors and metastatic LNs were successfully detected in the mice. In the clinical study, the efficacy of ICG was evaluated in 15 tumors and fifty-four LNs with suspected metastasis or anatomically key regional LNs. All 15 tumors were successfully detected. Among the fifty-four LNs, eleven were pathologically confirmed to have metastasis; all eleven were detected in ICG fluorescence imaging, with five in CT and seven in PET/CT. Furthermore, thirty-four LNs with no signals were pathologically confirmed as nonmetastatic. Intravenous injection of ICG may be a useful tool to detect metastatic LNs and tumors. However, ICG is not a targeting agent, and its relatively low fluorescence makes it difficult to use to detect tumors in vivo. Therefore, further studies are needed to develop contrast agents and devices that produce increased fluorescence signals.
Clinical application of functional near-infrared spectroscopy for burn assessment
Significance: Early assessment of local tissue oxygen saturation is essential for clinicians to determine the burn wound severity. Background: We assessed the burn extent and depth in the skin of the extremities using a custom-built 36-channel functional near-infrared spectroscopy system in patients with burns. Methods: A total of nine patients with burns were analyzed in this study. All second-degree burns were categorized as superficial, intermediate, and deep burns; non-burned skin on the burned side; and healthy skin on the contralateral non-burned side. Hemodynamic tissue signals from functional near-infrared spectroscopy attached to the burn site were measured during fNIRS using a blood pressure cuff. A nerve conduction study was conducted to check for nerve damage. Results: All second-degree burns were categorized into superficial, intermediate, and deep burns; non-burned skin on the burned side and healthy skin on the contralateral non-burned side showed a significant difference distinguishable using functional near-infrared spectroscopy. Hemodynamic measurements using functional near-infrared spectroscopy were more consistent with the diagnosis of burns 1 week later than that of the degree of burns diagnosed visually at the time of admission. Conclusion: Functional near-infrared spectroscopy may help with the early judgment of burn extent and depth by reflecting differences in the oxygen saturation levels in the skin.
Design and Testing of Augmented Reality-Based Fluorescence Imaging Goggle for Intraoperative Imaging-Guided Surgery
The different pathways between the position of a near-infrared camera and the user’s eye limit the use of existing near-infrared fluorescence imaging systems for tumor margin assessments. By utilizing an optical system that precisely matches the near-infrared fluorescence image and the optical path of visible light, we developed an augmented reality (AR)-based fluorescence imaging system that provides users with a fluorescence image that matches the real-field, without requiring any additional algorithms. Commercial smart glasses, dichroic beam splitters, mirrors, and custom near-infrared cameras were employed to develop the proposed system, and each mount was designed and utilized. After its performance was assessed in the laboratory, preclinical experiments involving tumor detection and lung lobectomy in mice and rabbits by using indocyanine green (ICG) were conducted. The results showed that the proposed system provided a stable image of fluorescence that matched the actual site. In addition, preclinical experiments confirmed that the proposed system could be used to detect tumors using ICG and evaluate lung lobectomies. The AR-based intraoperative smart goggle system could detect fluorescence images for tumor margin assessments in animal models, without disrupting the surgical workflow in an operating room. Additionally, it was confirmed that, even when the system itself was distorted when worn, the fluorescence image consistently matched the actual site.