Developing novel fluorescent probe for peroxynitrite: implication for understanding the roles of peroxynitrite and drug discovery in cerebral ischemia reperfusion injury

Session 7 - Oral PresentationsSTUDY GOAL: Peroxynitrite (ONOO‐) is a cytotoxic factor. As its short lifetime, ONOO‐ is hard to be detected in biological systems. This study aims to develop novel probe for detecting ONOO‐ and understand the roles of ONOO‐ in ischemic brains and drug discovery ABSTRACT: MitoPN‐1 was found to be a ONOO‐ specific probe with no toxicity. With MitoPN‐1, we studied the roles of ONOO‐ in hypoxic neuronal cells in vitro and MCAO …postprin

Retinal perfusion changes in radiation retinopathy-post brachytherapy for choroidal melanoma

Introduction: Radiation retinopathy (RR) is a chronic progressive vasculopathy developing secondary to the impact of ionizing radiation to the retina. RR develops post radiation therapy using radioactive plaque to treat intraocular tumors. It is not possible to predict which patients will develop RR. Changes in retinal blood oxygen saturation and blood flow could predict the future onset of RR, thereby facilitating the use of treatment such as intra-vitreal anti-vascular endothelial growth factor (VEGF). Methods: Chapter 3 and 4: Total retinal blood flow (TRBF) and retinal blood oxygen saturation (SO2) was non-invasively measured in eleven healthy human volunteers using a novel and exact provocation technique (RespirAct) that allows the precise control of the end-tidal partial pressure of oxygen (PETO2). Between-visits repeatability and within-visit variability of TRBF and SO2 measurements were assessed. Inner retinal oxygen delivery and consumption was calculated using Fick’s principle during stages of normoxia, hypoxia and hyperoxia. Chapter 5 and 6: Seventeen patients diagnosed with unilateral choroidal melanoma (CM) and eight patients who had developed unilateral ischemic RR were recruited from Ocular Oncology Clinic in the Princess Margaret Hospital, Toronto, Canada i.e. the only center all over Canada to treat CM patients with radiation therapy. The subjects underwent measurement of TRBF using a prototype methodology based upon Doppler Spectral Domain Optical Coherence Tomography (SD-OCT) and retinal vessel SO2 using a prototype Hyperspectral Retinal Camera (HRC), following pupil dilation with 1% tropicamide. In CM patients, the retinal hemodynamic parameters were studied in both eyes, before, 3months and 6months post 125Iodine plaque brachytherapy treatment. For RR patients, the measurements were taken once in both eyes after confirming the ischemic changes by wide-field fluorescein angiography. Results: Chapter 3 and 4: When the arterial PETO2 (end-tidal partial pressure of oxygen) was increased from baseline (PETO2=100mmHg) to 200 and 300mmHg, the TRBF significantly reduced (p=0.020) from 44.60 μL/min (+8.9) to 40.28 μL/min (+8.9) and 36.23 μL/min (+4.6), respectively. Retinal arteriolar SO2 (SaO2) did not show any significant change during PETO2 of 200 and 300mmHg, compared to baseline. However, retinal venular SO2 (SvO2) significantly increased (p<0.000) from 57.2% (+3.9) to 61.3% (+3.6) and 62.0% (+3.4) during PETO2 of 200 and 300mmHg, respectively, compared to baseline. Lowering the arterial PETO2, from baseline to 80, 60 and 50mmHg, TRBF significantly increased (p=0.040) from 43.17 μL/min (+12.7) to 45.19 μL/min (+5.5), 49.71 μL/min (+13.4) and 52.89 μL/min (+10.9) with simultaneous reduction in the SaO2 and SvO2 from 99.3 % (+ 5.8) and 56.3% (+ 4.2) to 95.6% (+ 5.1) and 52.5 (+ 4.1), 89.6% (+ 2.8) and 49.5% (+ 2.9), 83.3% (+ 3.9) and 45.0 % (+ 6.1), respectively (p<0.000). The group mean coefficient of repeatability (COR) for the retinal blood SaO2, SvO2 and TRBF were 18.4% (relative to a mean effect of 104.4%), 15.2% (relative to a mean effect of 60.3%), and 21.8 μL/min (relative to a mean effect of 44.72 μL/min). The overall coefficient of variability (COV) for SaO2, SvO2 and TRBF measurements were 4.7% and 6.9%, and, 15.1% respectively. The inner retinal oxygen extraction was calculated as 3.64 mLO2/min/100g tissue in humans. Chapter 5: The average TRBF in the eye with RR was significantly lower compared to the fellow eye (33.48 + 12.73 µL/min vs 50.37 + 15.26 µL/min; p = 0.013). The SaO2 and SvO2 was higher in the retinopathy eye compared to the fellow eye (101.11 + 4.26%, vs 94.45 + 5.79%; p=0.008) and (62.96 + 11.05% vs 51.24 + 6.88%, p=0.051), respectively. Chapter 6: Out of 17 CM patients recruited, 2 patient data was excluded due to poor image quality, and 3 others were lost to follow-up. During the six month follow up period, one person developed RR. The SaO2 measurement was found to be significantly increased (p=0.026) from 94.4 % (+7.9) to 98.9% (+8.8) and 100.6 % (+6.4), respectively during 3 and 6 month follow up post 125Iodine plaque brachytherapy compared to before treatment. Conclusions: Chapter 3: Our study demonstrated significant changes in retinal blood SO2 and TRBF during systemic changes in arterial PETO2. The variability in TRBF measurements may reflect the impact of subjective assessment in venous area estimation as well as Doppler signal strength differences between visits. One needs to note that, a common clinical test such as visual acuity measurement also has a reported variability of up to ±0.15 logMAR (or + 8 logMAR letters), relative to a mean effect of 0.017 logMAR (+ 4.2 letters), yet it is still being utilized as a useful clinical tool. The Doppler SD-OCT and HRC offer a quantifiable and repeatable technique of assessing retinal hemodynamics. Minimizing subjectivity in terms of blood flow analysis as well as correcting imperfections in the optics design of the HRC could possibly improve the repeatability of TRBF and retinal blood SO2, respectively. Chapter 4: Oxygen extracted from the inner retinal vessels remains unchanged during safe levels of systemic hypoxia and hyperoxia. Chapter 5: The effect of ionizing radiation has an impact on the TRBF and retinal blood SO2, clinically presenting similar to a rapidly developing diabetic retinopathy. The results show an altered retinal vascular physiology in patients with radiation related retinopathy. Chapter 6: 125Iodine brachytherapy significantly increases the retinal arteriolar blood SO2, suggesting improved retinal tissue perfusion in the treated eye. It is interesting to note that one patient developed RR in this six month period. About a 20% increase in retinal arteriolar and venular blood oxygen saturation was observed in this patient, 6 month post brachytherapy compared to pre-treatment value. In order to predict who will develop RR following brachytherapy, it is important to follow up rest of the eleven subjects to measure SO2 and TRBF during 12 and 18 month period or until they develop retinopathy. This will be a future work of interest, to recruit even large number of CM patients in a longitudinal approach. Only then a pattern or model for predicting RR in terms of SO2 or TRBF measurements could be established. The study examines the early effects of brachytherapy on retinal hemodynamics

Retinal Blood Flow and Vascular Reactivity in Chronic Smokers

Purpose To investigate the impact of cigarrete smoking in a group of otherwise healthy young individuals on: 1) Retinal blood flow using Doppler based SD-OCT, 2) Retinal vascular reactivity using a gas sequencer to provoke hypercapnia via constant changes in PETCO2 (end-tidal partial pressure of CO2) and in PETO2 (end-tidal partial pressure of O2). Methods An automated gas flow controller was used to achieve normoxic hypercapnia in ten non-smokers (mean age 28.9 yrs, SD 4.58) and nine smokers (mean age 27.55 yrs, SD 4.77). Retinal blood flow measurements were obtained using Doppler OCT and cannon laser blood flowmeter (CLBF) during baseline, normoxic hypercapnia (15% increase in PETCO2 relative to homeostatic baseline) and post-hypercapnia in both the groups. Exhaled carbon monoxide level was measured in all subjects. Results In non-smokers, retinal arteriolar diameter, blood velocity and flow increased by +4.1% (SD 2.8, p<0.0001), +16.7% (SD 14.6, p=0.0004) and +29.6% (SD 12.5, p<0.0001) respectively, during normoxic hypercapnia; Similarly, the venous area, venous velocity and total retinal blood flow increased by 7% (SD 8.6, p=0.0418), 18.1% (SD 20.8, p=0.0068) and 26% (SD 22.9, p<0.0001) respectively. In smokers, normoxic hypercapnia resulted in a significant increase in velocity by 12.0% (SD 6.2, p=0.0019) and flow by 14.6% (SD 9.5, p=0.0029); though arteriolar diameter increased by 1.7% (SD 1.7, p=0.2616), the result was not statistically significant. Total retinal blood flow increased significantly by 19.3% (SD 18.4, p=0.002) in response to normoxic hypercapnia. However, there was no significant difference in venous area (p=0.3322) and venous velocity measurements (p=0.1185) during hypercapnia compared to baseline and recovery. Comparing smokers and non-smokers, only the percentage change in arteriolar diameter (p=0.0379) and flow (p=0.0101) was significantly different among the groups. Group mean PETCO2 was increased by 15.9% in the non-smoking group and by 15.7% in the smoking group, with a concomitant increase in PETO2 by approximately 1.5 to 2% in both groups. There was no significant difference in baseline PETCO2 level between smokers and non-smokers. Conclusions Retinal vascular reactivity in response to normoxic hypercapnia is significantly reduced in young healthy individuals who smoke compared to non-smokers. Further studies are needed to elucidate the exact reason behind the impaired retinal autoregulation to provocative stimuli in smokers

Biomedical Photoacoustic Imaging and Sensing Using Affordable Resources

The overarching goal of this book is to provide a current picture of the latest developments in the capabilities of biomedical photoacoustic imaging and sensing in an affordable setting, such as advances in the technology involving light sources, and delivery, acoustic detection, and image reconstruction and processing algorithms. This book includes 14 chapters from globally prominent researchers , covering a comprehensive spectrum of photoacoustic imaging topics from technology developments and novel imaging methods to preclinical and clinical studies, predominantly in a cost-effective setting. Affordability is undoubtedly an important factor to be considered in the following years to help translate photoacoustic imaging to clinics around the globe. This first-ever book focused on biomedical photoacoustic imaging and sensing using affordable resources is thus timely, especially considering the fact that this technique is facing an exciting transition from benchtop to bedside. Given its scope, the book will appeal to scientists and engineers in academia and industry, as well as medical experts interested in the clinical applications of photoacoustic imaging

Correlated Multimodal Imaging in Life Sciences:Expanding the Biomedical Horizon

International audienceThe frontiers of bioimaging are currently being pushed toward the integration and correlation of several modalities to tackle biomedical research questions holistically and across multiple scales. Correlated Multimodal Imaging (CMI) gathers information about exactly the same specimen with two or more complementary modalities that-in combination-create a composite and complementary view of the sample (including insights into structure, function, dynamics and molecular composition). CMI allows to describe biomedical processes within their overall spatio-temporal context and gain a mechanistic understanding of cells, tissues, diseases or organisms by untangling their molecular mechanisms within their native environment. The two best-established CMI implementations for small animals and model organisms are hardware-fused platforms in preclinical imaging (Hybrid Imaging) and Correlated Light and Electron Microscopy (CLEM) in biological imaging. Although the merits of Preclinical Hybrid Imaging (PHI) and CLEM are well-established, both approaches would benefit from standardization of protocols, ontologies and data handling, and the development of optimized and advanced implementations. Specifically, CMI pipelines that aim at bridging preclinical and biological imaging beyond CLEM and PHI are rare but bear great potential to substantially advance both bioimaging and biomedical research. CMI faces three mai

Aerospace Medicine and Biology. A continuing bibliography with indexes, supplement 151

This bibliography lists 195 reports, articles, and other documents introduced into the NASA scientific and technical information system in January 1976

Brain Injury

The present two volume book "Brain Injury" is distinctive in its presentation and includes a wealth of updated information on many aspects in the field of brain injury. The Book is devoted to the pathogenesis of brain injury, concepts in cerebral blood flow and metabolism, investigative approaches and monitoring of brain injured, different protective mechanisms and recovery and management approach to these individuals, functional and endocrine aspects of brain injuries, approaches to rehabilitation of brain injured and preventive aspects of traumatic brain injuries. The collective contribution from experts in brain injury research area would be successfully conveyed to the readers and readers will find this book to be a valuable guide to further develop their understanding about brain injury

Fiber Optic Spectroscopy for the Optimization of Photodynamic Therapy

__Abstract__ Photodynamic therapy (PDT) is a treatment modality for cancer and premalignant lesions that utilizes a photoactive drug, the photosensitizer, in combination with light. PDT has become the treatment of choice for various malignancies. Furthermore, PDT is under investigation as a potential (palliative) treatment in situations where the possibilities of chemo-­ and radiotherapy are limited or exhausted. Since both photosensitizer and light have to be present to cause tissue damage, selective damage to the lesion can be achieved by controlling the presence of either one of them to the treatment area. Selective damage can be reached by i) choosing a photosensitizer that is mainly present in the lesion, or ii) preventing normal tissue from being illuminated. However, the success of PDT in reducing/removing (pre-­‐)malignant lesions has been variable. Treatment efficacy can range form non-‐observable effects to severe damage to normal tissue. Considering the complexity of both the execution of the treatment and damage pathways involved in PDT, some variability in treatment efficacy is not unexpected. However, given the fact that clinical applications of PDT that have proved successful remain small in number, more work is necessary to optimize therapeutic efficacy