Pub Date : 2024-08-09DOI: 10.1101/2024.08.07.607046
Yueming Zhuo, Mohajeet Balveer Bhuckory, Huakun Li, Hattori Junya, Davis Pham-Howard, David Veysset, Tong Ling, Daniel Palanker
Controlling the tissue temperature rise during retinal laser therapy is essential for predictable outcomes, especially at non-damaging settings. We demonstrate a method for determining the temperature rise in the retina using phase-resolved optical coherence tomography (pOCT) in vivo. Measurements based on the thermally induced optical path length changes (ΔOPL) in the retina during a 10-ms laser pulse allow detection of the temperature rise with a precision less than 1 °C, which is sufficient for calibration of the laser power for patient-specific non-damaging therapy. We observed a significant difference in confinement of the retinal deformations between the normal and the degenerate retina: in wild-type rats, thermal deformations are localized between the retinal pigment epithelium (RPE) and the photoreceptors' inner segments (IS), as opposed to a deep penetration of the deformations into the inner retinal layers in the degenerate retina. This implies the presence of a structural component within healthy photoreceptors that dampens the tissue expansion induced by the laser heating of the RPE and pigmented choroid. We hypothesize that the thin and soft cilium connecting the inner and outer segments (IS, OS) of photoreceptors may absorb the deformations of the OS and thereby preclude the tissue expansion further inward. Striking difference in the confinement of the retinal deformations induced by a laser pulse in healthy and degenerate retina may be used as a biomechanical diagnostic tool for the characterization of photoreceptor degeneration.
控制视网膜激光治疗过程中的组织温升对于获得可预测的治疗效果至关重要，尤其是在无损伤的情况下。我们展示了一种利用相位分辨光学相干断层扫描（pOCT）在体内确定视网膜温升的方法。根据 10 毫秒激光脉冲期间视网膜中的热诱导光路长度变化（ΔOPL）进行测量，可以检测到精度小于 1 °C的温升，这足以校准针对特定患者的非损伤性治疗的激光功率。我们观察到正常视网膜和变性视网膜在视网膜变形的局限性方面存在显著差异：在野生型大鼠中，热变形位于视网膜色素上皮（RPE）和感光器内节（IS）之间，而在变性视网膜中，变形则深入视网膜内层。这意味着在健康的感光体中存在一种结构成分，可以抑制激光加热 RPE 和色素脉络膜所引起的组织膨胀。我们假设，连接感光器内外节段（IS、OS）的薄而软的纤毛可吸收 OS 的变形，从而阻止组织进一步向内扩张。健康视网膜和变性视网膜在激光脉冲诱导的视网膜变形限制方面的惊人差异，可作为一种生物力学诊断工具，用于描述感光器变性的特征。
{"title":"Retinal thermometry in-vivo using phase-sensitive optical coherence tomography","authors":"Yueming Zhuo, Mohajeet Balveer Bhuckory, Huakun Li, Hattori Junya, Davis Pham-Howard, David Veysset, Tong Ling, Daniel Palanker","doi":"10.1101/2024.08.07.607046","DOIUrl":"https://doi.org/10.1101/2024.08.07.607046","url":null,"abstract":"Controlling the tissue temperature rise during retinal laser therapy is essential for predictable outcomes, especially at non-damaging settings. We demonstrate a method for determining the temperature rise in the retina using phase-resolved optical coherence tomography (pOCT) in vivo. Measurements based on the thermally induced optical path length changes (ΔOPL) in the retina during a 10-ms laser pulse allow detection of the temperature rise with a precision less than 1 °C, which is sufficient for calibration of the laser power for patient-specific non-damaging therapy. We observed a significant difference in confinement of the retinal deformations between the normal and the degenerate retina: in wild-type rats, thermal deformations are localized between the retinal pigment epithelium (RPE) and the photoreceptors' inner segments (IS), as opposed to a deep penetration of the deformations into the inner retinal layers in the degenerate retina. This implies the presence of a structural component within healthy photoreceptors that dampens the tissue expansion induced by the laser heating of the RPE and pigmented choroid. We hypothesize that the thin and soft cilium connecting the inner and outer segments (IS, OS) of photoreceptors may absorb the deformations of the OS and thereby preclude the tissue expansion further inward. Striking difference in the confinement of the retinal deformations induced by a laser pulse in healthy and degenerate retina may be used as a biomechanical diagnostic tool for the characterization of photoreceptor degeneration.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1101/2024.08.07.606992
Meisam Zaferani, Ryungeun Song, Ned S Wingreen, Howard A Stone, Sabine Petry
The self-organization of cytoskeletal networks in confined geometries requires sensing and responding to mechanical cues at nanometer to micron scales that allow for dynamic adaptation. Here, we show that the branching of microtubules (MTs) via branching MT nucleation combined with dynamic instability constitutes a boundary-sensing mechanism within confined spaces. Using a nanotechnology platform, we observe the self-organization of a branched MT network in a channel featuring a narrow junction and a closed end. Our observations reveal that branching MT nucleation occurs in the post-narrowing region only if that region exceeds a certain length before it terminates at the channel's closed end. The length-dependent occurrence of branching MT nucleation arises from the dynamic instability of existing MTs when they interact with the channel's closed end, combined with the specific timescale required for new MTs to nucleate at a point distant from the closed end, creating a mechanical feedback. Increasing the concentration of the base branching factor TPX2 accelerates nucleation kinetics and thus tunes the minimum length scale needed for occurrence of branching MT nucleation. As such, this feedback not only allows for adaptation to the local geometry, but also allows for tunable formation of MT networks in narrow (micron and submicron scale) channels. However, while a high concentration of TPX2 increases the kinetic rate of branching MT nucleation, it also stabilizes MTs at the channel's closed end leading to MT growth and nucleation in the reversed direction, and thus hinders boundary sensing. After experimental characterization of boundary-sensing feedback, we propose a minimal model and execute numerical simulations. We investigate how this feedback, wherein growing MTs dynamically sense their physical environment and provide nucleation sites for new MTs, sets a length/time scale that steers the architecture of MT networks in confined spaces. This "search-and-branch" mechanism has implications for the formation of MT networks during neuronal morphogenesis, including axonal growth and the formation of highly branched dendritic networks, as well as for plant development and MT-driven guidance in fungi, and engineering nanotechnologies.
{"title":"Boundary-Sensing Mechanism in Branched Microtubule Networks","authors":"Meisam Zaferani, Ryungeun Song, Ned S Wingreen, Howard A Stone, Sabine Petry","doi":"10.1101/2024.08.07.606992","DOIUrl":"https://doi.org/10.1101/2024.08.07.606992","url":null,"abstract":"The self-organization of cytoskeletal networks in confined geometries requires sensing and responding to mechanical cues at nanometer to micron scales that allow for dynamic adaptation. Here, we show that the branching of microtubules (MTs) via branching MT nucleation combined with dynamic instability constitutes a boundary-sensing mechanism within confined spaces. Using a nanotechnology platform, we observe the self-organization of a branched MT network in a channel featuring a narrow junction and a closed end. Our observations reveal that branching MT nucleation occurs in the post-narrowing region only if that region exceeds a certain length before it terminates at the channel's closed end. The length-dependent occurrence of branching MT nucleation arises from the dynamic instability of existing MTs when they interact with the channel's closed end, combined with the specific timescale required for new MTs to nucleate at a point distant from the closed end, creating a mechanical feedback. Increasing the concentration of the base branching factor TPX2 accelerates nucleation kinetics and thus tunes the minimum length scale needed for occurrence of branching MT nucleation. As such, this feedback not only allows for adaptation to the local geometry, but also allows for tunable formation of MT networks in narrow (micron and submicron scale) channels. However, while a high concentration of TPX2 increases the kinetic rate of branching MT nucleation, it also stabilizes MTs at the channel's closed end leading to MT growth and nucleation in the reversed direction, and thus hinders boundary sensing. After experimental characterization of boundary-sensing feedback, we propose a minimal model and execute numerical simulations. We investigate how this feedback, wherein growing MTs dynamically sense their physical environment and provide nucleation sites for new MTs, sets a length/time scale that steers the architecture of MT networks in confined spaces. This \"search-and-branch\" mechanism has implications for the formation of MT networks during neuronal morphogenesis, including axonal growth and the formation of highly branched dendritic networks, as well as for plant development and MT-driven guidance in fungi, and engineering nanotechnologies.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1101/2024.08.08.607178
Vinoin Devpaul Vincely, Carolyn L Bayer
Significance: Conventional spectral photoacoustic imaging (sPAI) to assess tissue oxygenation (sO2) uses optical wavelengths in the first near infrared window (NIR-I). This limits the maximum imaging depth (~1 cm) due to high spectral coloring of biological tissues. Aim: Second near infrared or short-wave infrared (NIR-II or SWIR) wavelengths (950-1400 nm) show potential for deep tissue sPAI due to the exponentially reduced tissue scattering and higher maximum exposure threshold (MPE) in this wavelength range. However, to date, a systematic assessment of NIR-II wavelengths for sPAI of tissue sO2 has yet to be performed. Approach: The NIR-II PA spectra of oxygenated and deoxygenated hemoglobin was first characterized using a phantom. Optimal wavelengths to minimize spectral coloring were identified. The resulting NIR-II PA imaging methods were then validated in vivo by measuring renal sO2 in adult female rats. Results: sPAI of whole blood under a phantom and of circulating renal blood in vivo, demonstrated PA spectra proportional to wavelength-dependent optical absorption. NIR-II wavelengths had a ~50% decrease in error of spectrally unmixed blood sO2 compared to conventional NIR-I wavelengths. In vivo measurements of renal sO2 validated these findings and demonstrated a ~30% decrease in error of estimated renal sO2 when using NIR-II wavelengths for spectral unmixing in comparison to NIR-I wavelengths. Conclusions: sPAI using NIR-II wavelengths improved the accuracy of tissue sO2 measurements. This is likely due to the overall reduced spectral coloring in this wavelength range. Combined with the increased safe skin exposure fluence limits in this wavelength range, demonstrate the potential to use NIR-II wavelengths for quantitative sPAI of sO2 from deep heterogeneous tissues.
{"title":"Improved Spectral Inversion of Blood Oxygenation due to Reduced Tissue Scattering: Towards NIR-II Photoacoustic Imaging","authors":"Vinoin Devpaul Vincely, Carolyn L Bayer","doi":"10.1101/2024.08.08.607178","DOIUrl":"https://doi.org/10.1101/2024.08.08.607178","url":null,"abstract":"<strong>Significance:</strong> Conventional spectral photoacoustic imaging (sPAI) to assess tissue oxygenation (sO<sub>2</sub>) uses optical wavelengths in the first near infrared window (NIR-I). This limits the maximum imaging depth (~1 cm) due to high spectral coloring of biological tissues. <strong>Aim:</strong> Second near infrared or short-wave infrared (NIR-II or SWIR) wavelengths (950-1400 nm) show potential for deep tissue sPAI due to the exponentially reduced tissue scattering and higher maximum exposure threshold (MPE) in this wavelength range. However, to date, a systematic assessment of NIR-II wavelengths for sPAI of tissue sO<sub>2</sub> has yet to be performed. <strong>Approach:</strong> The NIR-II PA spectra of oxygenated and deoxygenated hemoglobin was first characterized using a phantom. Optimal wavelengths to minimize spectral coloring were identified. The resulting NIR-II PA imaging methods were then validated in vivo by measuring renal sO<sub>2</sub> in adult female rats. <strong>Results:</strong> sPAI of whole blood under a phantom and of circulating renal blood in vivo, demonstrated PA spectra proportional to wavelength-dependent optical absorption. NIR-II wavelengths had a ~50% decrease in error of spectrally unmixed blood sO<sub>2</sub> compared to conventional NIR-I wavelengths. In vivo measurements of renal sO<sub>2</sub> validated these findings and demonstrated a ~30% decrease in error of estimated renal sO<sub>2</sub> when using NIR-II wavelengths for spectral unmixing in comparison to NIR-I wavelengths. <strong>Conclusions:</strong> sPAI using NIR-II wavelengths improved the accuracy of tissue sO<sub>2</sub> measurements. This is likely due to the overall reduced spectral coloring in this wavelength range. Combined with the increased safe skin exposure fluence limits in this wavelength range, demonstrate the potential to use NIR-II wavelengths for quantitative sPAI of sO<sub>2</sub> from deep heterogeneous tissues.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1101/2024.08.07.607023
Zachary T. Baumer, Matilda Newton, Lina Löfstrand, Genesis Nicole Carpio Paucar, Natalie G. Farny, Timothy A. Whitehead
For many enzymes, activity is regulated post-translationally by endogenous metabolites. Designing liganded control of essential activities like transcription would advance predictive control of biological processes, a fundamental goal of synthetic biology. Here we demonstrate that full-length, single subunit T7-derived RNA polymerases (T7 RNAP) can be controlled by physiologically relevant concentrations of indoles. We used rational design and directed evolution to identify T7 RNAP variants with minimal transcriptional activity in the absence of indole, and a 29-fold increase in activity with an EC50 of 344 µM. Indoles control T7-dependent gene expression exogenously, endogenously, and inter-cellularly. We also demonstrate indole-dependent bacteriophage viability and propagation in trans. Specificity of different indoles, T7 promoter specificities, and portability to different bacteria are shown. Our ligand activated RNA polymerases (LARPs) represent a new chemically inducible platform immediately deployable for novel synthetic biology applications, including for modulation of synthetic co-cultures.
{"title":"Dynamic regulation of engineered T7 RNA polymerases by endogenous metabolites","authors":"Zachary T. Baumer, Matilda Newton, Lina Löfstrand, Genesis Nicole Carpio Paucar, Natalie G. Farny, Timothy A. Whitehead","doi":"10.1101/2024.08.07.607023","DOIUrl":"https://doi.org/10.1101/2024.08.07.607023","url":null,"abstract":"For many enzymes, activity is regulated post-translationally by endogenous metabolites. Designing liganded control of essential activities like transcription would advance predictive control of biological processes, a fundamental goal of synthetic biology. Here we demonstrate that full-length, single subunit T7-derived RNA polymerases (T7 RNAP) can be controlled by physiologically relevant concentrations of indoles. We used rational design and directed evolution to identify T7 RNAP variants with minimal transcriptional activity in the absence of indole, and a 29-fold increase in activity with an EC<sub>50</sub> of 344 <em>µ</em>M. Indoles control T7-dependent gene expression exogenously, endogenously, and inter-cellularly. We also demonstrate indole-dependent bacteriophage viability and propagation in <em>trans</em>. Specificity of different indoles, T7 promoter specificities, and portability to different bacteria are shown. Our <span>l</span>igand <span>a</span>ctivated <span>R</span>NA <span>p</span>olymerases (LARPs) represent a new chemically inducible platform immediately deployable for novel synthetic biology applications, including for modulation of synthetic co-cultures.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1101/2024.08.05.606582
Ville Rimpiläinen, Alexandra Koulouri
Objective Unknown conductivities of the head tissues, particularly the skull, is a major factor of uncertainty in electroencephalography (EEG) source imaging. Here, we develop a personalized skull conductivity framework aiming to improve the head models used in the EEG source imaging and to reduce localization errors.
{"title":"Multimodal electrical impedance tomography and electroencephalography imaging: Does higher skull conductivity resolution in EIT imaging improve accuracy of EEG source localization?","authors":"Ville Rimpiläinen, Alexandra Koulouri","doi":"10.1101/2024.08.05.606582","DOIUrl":"https://doi.org/10.1101/2024.08.05.606582","url":null,"abstract":"<strong>Objective</strong> Unknown conductivities of the head tissues, particularly the skull, is a major factor of uncertainty in electroencephalography (EEG) source imaging. Here, we develop a personalized skull conductivity framework aiming to improve the head models used in the EEG source imaging and to reduce localization errors.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study focuses on addressing the challenges of dental implants in the geriatric population by enhancing the bioactivity of polyetheretherketone (PEEK) through surface modification. PEEK, with its elastic modulus close to alveolar bone, mitigates stress shielding but faces limitations in osseointegration due to low bioactivity. We introduced zinc (Zn) and metformin (MF) onto PEEK surfaces via a dopamine-assisted physical adhesion method, creating a functionalized derivative called ZnMF@PEEK. This combination targets diminished osteogenic potential, persistent inflammation, and cell senescence, which are common issues in elderly patients. Comprehensive physicochemical characterizations confirmed the successful preparation of ZnMF@PEEK, and in vitro and in vivo experiments systematically evaluated its biocompatibility and bioactivity. The results indicate that ZnMF@PEEK holds promise as a dental implant material tailored to the specific needs of the elderly, addressing multifaceted challenges in osseointegration.
{"title":"Zinc and Metformin Co-Functionalized Polyetheretherketone: A Novel Dental Implant Material Tailored for the Elderly","authors":"Zhengwei Liu, Enze Zhao, Hanwei Huang, Yuxun Wu, Yicong He, Shuting Bai, Suwen Wang, Shirou Fan, Shuaishuai Cao, Bin Tang, Yansong Wang","doi":"10.1101/2024.08.05.606613","DOIUrl":"https://doi.org/10.1101/2024.08.05.606613","url":null,"abstract":"This study focuses on addressing the challenges of dental implants in the geriatric population by enhancing the bioactivity of polyetheretherketone (PEEK) through surface modification. PEEK, with its elastic modulus close to alveolar bone, mitigates stress shielding but faces limitations in osseointegration due to low bioactivity. We introduced zinc (Zn) and metformin (MF) onto PEEK surfaces via a dopamine-assisted physical adhesion method, creating a functionalized derivative called ZnMF@PEEK. This combination targets diminished osteogenic potential, persistent inflammation, and cell senescence, which are common issues in elderly patients. Comprehensive physicochemical characterizations confirmed the successful preparation of ZnMF@PEEK, and in <em>vitro</em> and in <em>vivo</em> experiments systematically evaluated its biocompatibility and bioactivity. The results indicate that ZnMF@PEEK holds promise as a dental implant material tailored to the specific needs of the elderly, addressing multifaceted challenges in osseointegration.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1101/2024.08.04.606502
Kaiyuan Liu, Ruixue Wang, Longqian Huang, Huiying Zhang, Mengqin Gao, Bin Sun, Yizhou Tan, Juan Ye, Zhihua Ding, Ying Gu, Shaomin Zhang, Peng Li
The early detection of premotor Parkinson’s disease (PD) is important for initiating neuroprotective interventions prior to the widespread and irreversible loss of dopaminergic (DAergic) neurons. We propose a novel optical functional approach for detecting premotor PD from the retina by using functional OCT angiography (fOCTA) to measure PD-related changes in retinal neurovascular coupling (rNVC) at the capillary level, termed fOCTA-rNVC. We demonstrated that, likely due to the retinal DAergic degeneration, functional rNVC was attenuated and delayed in premotor PD mice, whereas no significant change in the retinal structure was found. Furthermore, the administration of levodopa reversed PD-related rNVC attenuation in premotor PD mice, whereas no recovery in ageing-related attenuation in aged mice without significant DAergic deficits was observed. On the basis of the levodopa recoverability of attenuated capillary rNVC, we achieved a remarkable accuracy of ∼100% in detecting premotor PD mice with ∼14.1% loss of midbrain DAergic neurons. These findings suggest that fOCTA-rNVC can be applied for the noninvasive and accurate detection of premotor PD, offering a cost-effective solution with improved accessibility and convenience for large-scale screening.
在多巴胺能（DAergic）神经元出现广泛且不可逆的丧失之前，早期检测帕金森病（PD）的运动前期对于启动神经保护干预措施非常重要。我们提出了一种从视网膜检测运动前痴呆症的新型光学功能方法，利用功能性 OCT 血管造影术（fOCTA）在毛细血管水平测量痴呆症相关的视网膜神经血管耦合（rNVC）变化，称为 fOCTA-rNVC。我们发现，可能是由于视网膜DA能变性，运动前期帕金森病小鼠的功能性rNVC减弱并延迟，而视网膜结构未发现明显变化。此外，左旋多巴可逆转运动前期帕金森病小鼠与帕金森病相关的rNVC衰减，而在无明显DA能缺陷的老年小鼠中，未观察到与衰老相关的衰减恢复。根据左旋多巴对毛细血管rNVC衰减的可恢复性，我们在检测中脑DA能神经元缺失14.1%的运动前期PD小鼠方面达到了惊人的100%的准确率。这些研究结果表明，fOCTA-rNVC 可用于无创、准确地检测运动前期帕金森病，为大规模筛查提供了一种具有成本效益的解决方案，并提高了可及性和便利性。
{"title":"Transocular detection of premotor Parkinson’s disease via retinal neurovascular coupling through functional OCT angiography","authors":"Kaiyuan Liu, Ruixue Wang, Longqian Huang, Huiying Zhang, Mengqin Gao, Bin Sun, Yizhou Tan, Juan Ye, Zhihua Ding, Ying Gu, Shaomin Zhang, Peng Li","doi":"10.1101/2024.08.04.606502","DOIUrl":"https://doi.org/10.1101/2024.08.04.606502","url":null,"abstract":"The early detection of premotor Parkinson’s disease (PD) is important for initiating neuroprotective interventions prior to the widespread and irreversible loss of dopaminergic (DAergic) neurons. We propose a novel optical functional approach for detecting premotor PD from the retina by using functional OCT angiography (fOCTA) to measure PD-related changes in retinal neurovascular coupling (rNVC) at the capillary level, termed fOCTA-rNVC. We demonstrated that, likely due to the retinal DAergic degeneration, functional rNVC was attenuated and delayed in premotor PD mice, whereas no significant change in the retinal structure was found. Furthermore, the administration of levodopa reversed PD-related rNVC attenuation in premotor PD mice, whereas no recovery in ageing-related attenuation in aged mice without significant DAergic deficits was observed. On the basis of the levodopa recoverability of attenuated capillary rNVC, we achieved a remarkable accuracy of ∼100% in detecting premotor PD mice with ∼14.1% loss of midbrain DAergic neurons. These findings suggest that fOCTA-rNVC can be applied for the noninvasive and accurate detection of premotor PD, offering a cost-effective solution with improved accessibility and convenience for large-scale screening.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The quantification of cardiac strains as structural indices of cardiac function has a growing prevalence in clinical diagnosis. However, the highly heterogeneous four-dimensional (4D) cardiac motion challenges accurate “regional” strain quantification and leads to sizable differences in the estimated strains depending on the imaging modality and post-processing algorithm, limiting the translational potential of strains as incremental biomarkers of cardiac dysfunction. There remains a crucial need for a feasible benchmark that successfully replicates complex 4D cardiac kinematics to determine the reliability of strain calculation algorithms. In this study, we propose an in-silico heart phantom derived from finite element (FE) simulations to validate the quantification of 4D regional strains. First, as a proof-of-concept exercise, we created synthetic magnetic resonance (MR) images for a hollow thick-walled cylinder under pure torsion with an exact solution and demonstrated that “ground-truth” values can be recovered for the twist angle, which is also a key kinematic index in the heart. Next, we used mouse-specific FE simulations of cardiac kinematics to synthesize dynamic MR images by sampling various sectional planes of the left ventricle (LV). Strains were calculated using our recently developed non-rigid image registration (NRIR) framework in both problems. Moreover, we studied the effects of image quality on distorting regional strain calculations by conducting in-silico experiments for various LV configurations. Our studies offer a rigorous and feasible tool to standardize regional strain calculations to improve their clinical impact as incremental biomarkers.
{"title":"In-silico heart model phantom to validate cardiac strain imaging","authors":"Tanmay Mukherjee, Muhammad Usman, Rana Raza Mehdi, Emilio Mendiola, Jacques Ohayon, Diana Lindquist, Dipan Shah, Sakthivel Sadayappan, Roderic Pettigrew, Reza Avazmohammadi","doi":"10.1101/2024.08.05.606672","DOIUrl":"https://doi.org/10.1101/2024.08.05.606672","url":null,"abstract":"The quantification of cardiac strains as structural indices of cardiac function has a growing prevalence in clinical diagnosis. However, the highly heterogeneous four-dimensional (4D) cardiac motion challenges accurate “regional” strain quantification and leads to sizable differences in the estimated strains depending on the imaging modality and post-processing algorithm, limiting the translational potential of strains as incremental biomarkers of cardiac dysfunction. There remains a crucial need for a feasible benchmark that successfully replicates complex 4D cardiac kinematics to determine the reliability of strain calculation algorithms. In this study, we propose an in-silico heart phantom derived from finite element (FE) simulations to validate the quantification of 4D regional strains. First, as a proof-of-concept exercise, we created synthetic magnetic resonance (MR) images for a hollow thick-walled cylinder under pure torsion with an exact solution and demonstrated that “ground-truth” values can be recovered for the twist angle, which is also a key kinematic index in the heart. Next, we used mouse-specific FE simulations of cardiac kinematics to synthesize dynamic MR images by sampling various sectional planes of the left ventricle (LV). Strains were calculated using our recently developed non-rigid image registration (NRIR) framework in both problems. Moreover, we studied the effects of image quality on distorting regional strain calculations by conducting in-silico experiments for various LV configurations. Our studies offer a rigorous and feasible tool to standardize regional strain calculations to improve their clinical impact as incremental biomarkers.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1101/2024.08.05.606686
Tarek E. Moustafa, Rachel L. Belote, Edward R. Polanco, Robert L. Judson-Torres, Thomas A. Zangle
Significance Measuring changes in cellular structure and organelles is crucial for understanding disease progression and cellular responses to treatments. A label-free imaging method can aid in advancing biomedical research and therapeutic strategies.
{"title":"Quadrant darkfield (QDF) for label-free imaging of intracellular puncta","authors":"Tarek E. Moustafa, Rachel L. Belote, Edward R. Polanco, Robert L. Judson-Torres, Thomas A. Zangle","doi":"10.1101/2024.08.05.606686","DOIUrl":"https://doi.org/10.1101/2024.08.05.606686","url":null,"abstract":"<strong>Significance</strong> Measuring changes in cellular structure and organelles is crucial for understanding disease progression and cellular responses to treatments. A label-free imaging method can aid in advancing biomedical research and therapeutic strategies.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"368 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1101/2024.08.05.606733
Ye Eun Song, Noah Eckman, Samya Sen, Olivia M. Saouaf, Eric A. Appel
Hydrogels have emerged as promising materials for bioprinting and many other biomedical applications due to their high degree of biocompatibility and ability to support and/or modulate cell viability and function. Yet, many hydrogel bioinks have suffered from low efficiency due to limitations on accessible printing speeds, often limiting cell viability and/or the constructs which can be generated. In this study, we report a highly extensible bioink system created by modulating the rheology of physically crosslinked hydrogels comprising hydrophobically modified cellulosic biopolymers and additives such as surfactants or cyclodextrins. We demonstrate that these hydrogel materials are highly shear-thinning with broadly tunable viscoelasticity and stress-relaxation behaviors through simple modulation of the composition of the additives. Rheological experiments demonstrate that increasing concentration of rheology-modifying additives yields hydrogel materials exhibiting extensional strain-to-break values up to 2000%. We demonstrate the potential of these hydrogels for use as bioinks by evaluating the relationship between extensibility and printability, demonstrating that greater hydrogel extensibility enables faster print speeds and smaller print features. Our findings suggest that optimizing hydrogel extensibility can enhance high-speed 3D bioprinting capabilities.
{"title":"Highly extensible physically crosslinked hydrogels for high-speed 3D bioprinting","authors":"Ye Eun Song, Noah Eckman, Samya Sen, Olivia M. Saouaf, Eric A. Appel","doi":"10.1101/2024.08.05.606733","DOIUrl":"https://doi.org/10.1101/2024.08.05.606733","url":null,"abstract":"Hydrogels have emerged as promising materials for bioprinting and many other biomedical applications due to their high degree of biocompatibility and ability to support and/or modulate cell viability and function. Yet, many hydrogel bioinks have suffered from low efficiency due to limitations on accessible printing speeds, often limiting cell viability and/or the constructs which can be generated. In this study, we report a highly extensible bioink system created by modulating the rheology of physically crosslinked hydrogels comprising hydrophobically modified cellulosic biopolymers and additives such as surfactants or cyclodextrins. We demonstrate that these hydrogel materials are highly shear-thinning with broadly tunable viscoelasticity and stress-relaxation behaviors through simple modulation of the composition of the additives. Rheological experiments demonstrate that increasing concentration of rheology-modifying additives yields hydrogel materials exhibiting extensional strain-to-break values up to 2000%. We demonstrate the potential of these hydrogels for use as bioinks by evaluating the relationship between extensibility and printability, demonstrating that greater hydrogel extensibility enables faster print speeds and smaller print features. Our findings suggest that optimizing hydrogel extensibility can enhance high-speed 3D bioprinting capabilities.","PeriodicalId":501308,"journal":{"name":"bioRxiv - Bioengineering","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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