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Detection of Pre-Malignant Gastrointestinal Lesions Using Surface-Enhanced Resonance Raman Scattering-Nanoparticle Endoscopy
摘要： Cancers of the gastrointestinal (GI) tract are among the most frequent and most lethal cancers worldwide. An important reason for this high mortality is that early disease is typically asymptomatic, and patients often present with advanced, incurable disease. Even in high-risk patients who routinely undergo endoscopic screening, lesions can be missed due to their small size or subtle appearance. Thus, current imaging approaches lack the sensitivity and specificity to accurately detect incipient GI tract cancers. Here we report our finding that a single dose of a high-sensitivity surface-enhanced resonance Raman scattering nanoparticle (SERRS-NP) enables reliable detection of pre-cancerous GI lesions in animal models that closely mimic disease development in humans. Some of these animal models have not been used previously to evaluate imaging probes for early cancer detection. The studies were performed using a commercial Raman imaging system, a newly-developed mouse Raman endoscope, and finally a clinically applicable Raman endoscope for larger animal studies. We show that this SERRS-NP-based approach enables robust detection of small, pre-malignant lesions in animal models that faithfully recapitulate human esophageal, gastric, and colorectal tumorigenesis. This method holds promise for much earlier detection of GI cancers than currently possible and could lead therefore to marked reduction of morbidity and mortality of these tumor types.
关键词： cancer,Raman,endoscopy,preclinical,early detection,nanoparticle
更新于2025-09-23 15:23:52
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Discovery of [ <sup>18</sup> F]PSMA-7, a novel PET-probe for the detection of small PSMA positive lesions
摘要： Prostate specific membrane antigen (PSMA) expressed by the vast majority of prostate cancers (PCa) is a promising target for PCa imaging. The application of PSMA specific 18F-labeled PET probes like 18F-DCFPyL and 18F-PSMA-1007 considerably improved the accuracy of PCa tumor detection. However, there remains a need for further improvements regarding sensitivity and specificity. The aim of this study was the development of highly selective and specific PSMA probes with enhanced imaging properties, in comparison with 18F-DCFPyL, 18F-PSMA-1007 and 68Ga-PSMA-11. Methods: Eight novel 18F-labeled PSMA ligands were prepared. Their cellular uptake in PSMA+ LNCaP C4-2 and PSMA– PC-3 cells was compared to that of 18F-DCFPyL. The most promising candidates were additionally evaluated by μPET in healthy rats using PSMA+ peripheral ganglia as a model for small PCa lesions. PET images of the ligand with the best outcome, 18F-JK-PSMA-7, were compared to those of 18F-DCFPyL, 18F-PSMA-1007 and 68Ga-PSMA-11 with respect to key image quality parameters for the time frame 60-120 min. Results: Compared to 18F-DCFPyL, 18F-JK-PSMA-7 demonstrated increased PSMA specific cellular uptake. While target-to-background ratios of 18F-DCFPyL and 18F-PSMA-1007 were comparable, this parameter was higher for 18F-JK-PSMA-7 and lower for 68Ga-PSMA-11. Image acutance was significantly higher for 18F-JK-PSMA-7 and 18F-PSMA-1007 compared to 18F-DCFPyL and 68Ga-PSMA-11. Image resolution was similar for all four tracers. 18F-PSMA-1007 demonstrated significantly higher blood protein binding and bone uptake than the other tracers. Conclusion: 18F-JK-PSMA-7 is a promising candidate for high quality visualization of small PSMA-positive lesions. Excellent preclinical imaging properties justify further preclinical and clinical studies of this tracer.
关键词： Prostate carcinoma,PSMA,preclinical model,radiofluorination,positron emission tomography,imaging
更新于2025-09-23 15:21:01
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Ultrahigh Resolution Mouse Optical Coherence Tomography to Aid Intraocular Injection in Retinal Gene Therapy Research
摘要： HR-SD-OCT is utilized to monitor the progression of photoreceptor degeneration in live mouse models, assess the delivery of therapeutic agents into the subretinal space, and to evaluate toxicity and efficacy in vivo. HR-SD-OCT uses near infrared light (800-880 nm) and has optics specifically designed for the unique optics of the mouse eye with sub-2-micron axial resolution. Transgenic mouse models of outer retinal (photoreceptor) degeneration and controls were imaged to assess the disease progression. Pulled glass microneedles were used to deliver sub retinal injections of adeno-associated virus (AAV) or nanoparticles (NP) via a trans-scleral and trans-choroidal approach. Careful positioning of the needle into the subretinal space was required prior to a calibrated pressure injection, which delivers fluid into the sub retinal space. Real time subretinal surgery was conducted on our retinal imaging system (RIS). HR-SD-OCT demonstrated progressive uniform retinal degeneration due to expression of a toxic mutant human mutant rhodopsin (P347S) (RHOP347S) transgene in mice. HR-SD-OCT allows rigorous quantification of all the retinal layers. Outer nuclear layer (ONL) thickness and photoreceptor outer segment length (OSL) measurements correlate with photoreceptor vitality, degeneration, or rescue. The RIS delivery system allows real-time visualization of subretinal injections in neonatal (~P10-14) or adult mice, and HR-SD-OCT immediately determines success of delivery and maps areal extent. HR-SD-OCT is a powerful tool that can evaluate the success of subretinal surgery in mice, in addition to measuring vitality of photoreceptors in vivo. HR-SD-OCT can also be used to identify uniform animal cohorts to evaluate the extent of retinal degeneration, toxicity, and therapeutic rescue in preclinical gene therapy research studies.
关键词： Optical Coherence Tomography,Retinal Degeneration,Imaging,Real-time,Retina,Microscope,Intraocular Injection,Preclinical,In Vivo,Photoreceptors,Greenough Stereo Microscopy,Sub-retinal
更新于2025-09-23 15:21:01
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Dual layer doI detector modules for a dedicated mouse brain PET/MRI
摘要： This work discusses two system geometries including their associated block detectors. Both configurations were based on a dual layer offset structure with small crystals sizes, in the order of 1×1×4/6 mm3, to provide discrete depth of interaction information. The detector for configuration “A” was based on a 4×4 silicon photomultiplier (SiPM) array attached to an optical diffusor, and a 12×12 as well as a 9×11 LSO crystal array, to achieve optimal system sensitivity. This configuration was evaluated by a double layer of 12×12 crystals. Configuration “B” was composed of three 2×2 SiPM arrays equipped with a 1 mm diffusor to read out an LSO stack of 20×6 and 19×5 individual crystals. The average peak-to-valley ratio of the inner/outer layer was 3.5/3.6 for detector “A”, and 3.4/2.8 for detector “B”. The average full width at half maximum (FWHM) energy resolution of the block detectors were 22.24±3.36% for “A” and 30.67±5.37% for “B”. The FWHM of the full block timing resolution of the inner/outer layer was 1.4 ns/1.2 ns for detector “A” and 1.8 ns/1.4 ns for “B”. The performance of the crystal position profile, the energy, and timing resolution indicate that configuration “A” is more appropriate for a mouse brain PET/MRI system.
关键词： PET/MRI,Depth of interaction,brain,small animal brain imaging,PET/RF,integrated MRI-coil,preclinical imaging,PET
更新于2025-09-19 17:15:36
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Low-level laser therapy (LLLT) in sites grafted with osteoconductive bone substitutes improves osseointegration
摘要： The aim of this study was to evaluate the osseointegration of implants placed in areas grafted with different osteoconductive bone substitutes irradiated with infrared low-level laser therapy (LLLT). Fifty-six rats were randomly allocated into 4 groups: DBB, bone defects filled with deproteinized bovine bone graft (DBB); HA/TCP, bone defects filled with biphasic ceramic made of hydroxyapatite and β-tricalcium phosphate (HA/TCP); DBB-L, bone defects filled with DBB and treated by LLLT; HA/TCP-L, bone defects filled with HA/TCP and treated by LLLT. Bone defects were performed in the tibia of each animal and filled with the different biomaterials. The grafted areas were treated with LLLT (λ 808 nm, 100 mW, ? ～ 0.60 mm) in 7 sessions with 48 h between the irradiations. After the 60-day period, the implants were placed, and the animals were euthanized after 15 and 45 days. The osseointegration and bone repair in the grafted area were evaluated by biomechanical, microtomographic and histometric analyses, and the expression of some bone biomarkers was evaluated by immunohistochemistry analysis. LLLT induced higher degree of osseointegration, which was associated with the greater expression of BMP2 and OCN. LLLT performed in areas grafted with osteoconductive bone substitutes prior to implant placement improves osseointegration.
关键词： Osseointegration,Preclinical study,Bone substitutes,Low-level laser therapy
更新于2025-09-19 17:13:59
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Lasers in Spine Surgery
摘要： Laser spine surgery has been a focus of intense interest in the lay press and among patients. On the Internet, a host of purported benefits to laser surgery exists. Lasers have long been used in pain management procedures such as percutaneous diskectomy. However, a few published articles are available on lasers in conventional spine surgery. From our review of the literature, the purported advantages of lasers, such as reduced inflammation and degeneration, are not been supported by preclinical research. The available clinical studies do not show a notable advantage for laser surgery. Moreover, the low enrollment, nonblinded, retrospective studies that are available are heavily subject to bias. The documented advantages of laser spine surgery described in the research studies are not consistent with the public’s impression of its purported benefits. Furthermore, laser-specific complications are present about which patients should be informed. On the basis of the current research, we conclude that lasers add distinct potential complications without any corresponding clinical benefit. Because of the public interest, we feel that this is an important topic for the general orthopaedic community.
关键词： Complications,Percutaneous diskectomy,Clinical studies,Preclinical research,Laser spine surgery
更新于2025-09-12 10:27:22
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Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration
摘要： Background: Cell-based regenerative medicine therapies are now frequently tested in clinical trials. In many conditions, cell therapies are administered systemically, but there is little understanding of their fate, and adverse events are often under-reported. Currently, it is only possible to assess safety and fate of cell therapies in preclinical studies, specifically by monitoring animals longitudinally using multi-modal imaging approaches. Here, using a suite of in vivo imaging modalities to explore the fate of a range of human and murine cells, we investigate how route of administration, cell type and host immune status affect the fate of administered cells. Methods: We applied a unique imaging platform combining bioluminescence, optoacoustic and magnetic resonance imaging modalities to assess the safety of different human and murine cell types by following their biodistribution and persistence in mice following administration into the venous or arterial system. Results: Longitudinal imaging analyses (i) suggested that the intra-arterial route may be more hazardous than intravenous administration for certain cell types, (ii) revealed that the potential of a mouse mesenchymal stem/stromal cell (MSC) line to form tumours depended on administration route and mouse strain and (iii) indicated that clinically tested human umbilical cord (hUC)-derived MSCs can transiently and unexpectedly proliferate when administered intravenously to mice. Conclusions: In order to perform an adequate safety assessment of potential cell-based therapies, a thorough understanding of cell biodistribution and fate post administration is required. The non-invasive imaging platform used here can expose not only the general organ distribution of these therapies, but also a detailed view of their presence within different organs and, importantly, tumourigenic potential. Our observation that the hUC-MSCs but not the human bone marrow (hBM)-derived MSCs persisted for a period in some animals suggests that therapies with these cells should proceed with caution.
关键词： Safety,Mesenchymal stem/stromal cells,Preclinical models,Multi-modal imaging,Cell therapies,Cell tracking
更新于2025-09-11 14:15:04
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High-speed quantitative 3D imaging by dual-illumination holographic microscopy
摘要： A new blood flow imaging (BFI) technique using digital holography with double illumination of the sample is proposed. We imaged the moving red blood cells (RBCs) using a two microscope objective lenses setup. The setup consists in a larger angle of separation (90 (cid:1)) between the two illumination beams, allowing a wider angular rotation at good z resolution. Moreover, the setup geometry allows an easier displacement of the sample in all directions. Results show that this technique is able to perform phase-shifting reconstruction for the two beams at the same time which is more suitable for the future implementation of live 3D holography. Experimental results are carried out for the verification of the effectiveness of the proposed technique on a zebrafish larvae sample.
关键词： preclinical models,red blood cells,fish embryo,holography,microcirculation
更新于2025-09-09 09:28:46