Aerosol delivery during invasive mechanical ventilation: development of a preclinical ex vivo respiratory model for aerosol regional deposition

AbstractIn intensive care units, nebulization is a usual route for drug administration to patients under mechanical ventilation (MV). The effectiveness of inhalation devices as well as depositions sites of aerosols for ventilated patients remain poorly documented. In vivo human inhalation studies are scarce due to ethical restrictions because imaging techniques require radioaerosols to assess regional aerosol deposition. Thus, we developed an ex vivo respiratory model under invasive MV for preclinical aerosol deposition studies. The model was composed of ex vivo porcine respiratory tracts. MV was achieved thanks to a tracheal intubation and a medical ventilator under controlled conditions. Respiratory features were studied using analogical sensors. Then regional homogeneity of gas-ventilation was assessed with 81mKrypton scintigraphies. Finally, a proof of concept study for aerosol deposition was performed. Obtained respiratory features as well as gamma-imaging techniques, which demonstrated a homogenous regional ventilation and about 18% ± 4% of the nebulized dose deposited the respiratory tract, were in good agreement with human data available in the literature. This original ex vivo respiratory model provides a feasible, reproducible and cost-effective preclinical tool to achieve aerosol deposition studies under MV.

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In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

Molecular Imaging ◽

10.2310/7290.2005.05133 ◽

2005 ◽

Vol 4 (4) ◽

pp. 7290.2005.05133 ◽

Cited By ~ 19

Author(s):

Matthew J. Hardwick ◽

Ming-Kai Chen ◽

Kwamena Baidoo ◽

Martin G. Pomper ◽

Tomás R. Guilarte

Keyword(s):

In Vivo Imaging ◽

Ex Vivo ◽

Inflammatory Diseases ◽

Imaging Techniques ◽

Benzodiazepine Receptors ◽

Small Animal ◽

Small Animal Pet ◽

Planar Imaging ◽

Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

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EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases

EJNMMI Research ◽

10.1186/s13550-021-00820-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Erik H. J. G. Aarntzen ◽

Edel Noriega-Álvarez ◽

Vera Artiko ◽

André H. Dias ◽

Olivier Gheysens ◽

...

Keyword(s):

Molecular Imaging ◽

Radionuclide Imaging ◽

Musculoskeletal Diseases ◽

Ex Vivo ◽

Imaging Techniques ◽

Large Body ◽

Therapeutic Interventions ◽

Histopathological Analysis ◽

Complementary Value

AbstractInflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.

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Towards Clinical Translation of LED-Based Photoacoustic Imaging: A Review

Sensors ◽

10.3390/s20092484 ◽

2020 ◽

Vol 20 (9) ◽

pp. 2484 ◽

Cited By ~ 10

Author(s):

Yunhao Zhu ◽

Ting Feng ◽

Qian Cheng ◽

Xueding Wang ◽

Sidan Du ◽

...

Keyword(s):

Ex Vivo ◽

Photoacoustic Imaging ◽

Imaging Techniques ◽

Clinical Translation ◽

Key Factors ◽

Pilot Studies ◽

History Of ◽

Molecular Components ◽

Clinical Potential

Photoacoustic imaging, with the capability to provide simultaneous structural, functional, and molecular information, is one of the fastest growing biomedical imaging modalities of recent times. As a hybrid modality, it not only provides greater penetration depth than the purely optical imaging techniques, but also provides optical contrast of molecular components in the living tissue. Conventionally, photoacoustic imaging systems utilize bulky and expensive class IV lasers, which is one of the key factors hindering the clinical translation of this promising modality. Use of LEDs which are portable and affordable offers a unique opportunity to accelerate the clinical translation of photoacoustics. In this paper, we first review the development history of LED as an illumination source in biomedical photoacoustic imaging. Key developments in this area, from point-source measurements to development of high-power LED arrays, are briefly discussed. Finally, we thoroughly review multiple phantom, ex-vivo, animal in-vivo, human in-vivo, and clinical pilot studies and demonstrate the unprecedented preclinical and clinical potential of LED-based photoacoustic imaging.

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Real-Time Optical Monitoring of Endotracheal Tube Displacement

Biosensors ◽

10.3390/bios10110174 ◽

2020 ◽

Vol 10 (11) ◽

pp. 174

Author(s):

Ramzan Ullah ◽

Karl Doerfer ◽

Pawjai Khampang ◽

Faraneh Fathi ◽

Wenzhou Hong ◽

...

Keyword(s):

Endotracheal Tube ◽

Real Time ◽

Near Infrared ◽

Ex Vivo ◽

Light Emitting Diode ◽

Clinical Care ◽

Cost Effective ◽

Infrared Light ◽

In Vivo Experiments

Proper ventilation of a patient with an endotracheal tube (ETT) requires proper placement of the ETT. We present a sensitive, noninvasive, operator-free, and cost-effective optical sensor, called Opt-ETT, for the real-time assessment of ETT placement and alerting of the clinical care team should the ETT become displaced. The Opt-ETT uses a side-firing optical fiber, a near-infrared light-emitting diode, two photodetectors with an integrated amplifier, an Arduino board, and a computer loaded with a custom LabVIEW program to monitor the position of the endotracheal tube inside the windpipe. The Opt-ETT generates a visual and audible warning if the tube moves over a distance set by the operator. Displacement prediction is made using a second-order polynomial fit to the voltages measured from each detector. The system is tested on ex vivo porcine tissues, and the accuracy is determined to be better than 1.0 mm. In vivo experiments with a pig are conducted to test the performance and usability of the system.

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Image-based modelling of skeletal muscle oxygenation

Journal of The Royal Society Interface ◽

10.1098/rsif.2016.0992 ◽

2017 ◽

Vol 14 (127) ◽

pp. 20160992 ◽

Cited By ~ 7

Author(s):

B. Zeller-Plumhoff ◽

T. Roose ◽

G. F. Clough ◽

P. Schneider

Keyword(s):

Skeletal Muscle ◽

Blood Vessel ◽

Ex Vivo ◽

Imaging Techniques ◽

Muscle Oxygenation ◽

Skeletal Muscle Oxygenation ◽

Health And Disease ◽

Vessel Networks

The supply of oxygen in sufficient quantity is vital for the correct functioning of all organs in the human body, in particular for skeletal muscle during exercise. Disease is often associated with both an inhibition of the microvascular supply capability and is thought to relate to changes in the structure of blood vessel networks. Different methods exist to investigate the influence of the microvascular structure on tissue oxygenation, varying over a range of application areas, i.e. biological in vivo and in vitro experiments, imaging and mathematical modelling. Ideally, all of these methods should be combined within the same framework in order to fully understand the processes involved. This review discusses the mathematical models of skeletal muscle oxygenation currently available that are based upon images taken of the muscle microvasculature in vivo and ex vivo . Imaging systems suitable for capturing the blood vessel networks are discussed and respective contrasting methods presented. The review further informs the association between anatomical characteristics in health and disease. With this review we give the reader a tool to understand and establish the workflow of developing an image-based model of skeletal muscle oxygenation. Finally, we give an outlook for improvements needed for measurements and imaging techniques to adequately investigate the microvascular capability for oxygen exchange.

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Comparison of optical coherence tomography and high frequency ultrasound imaging in mice for the assessment of skin morphology and intradermal volumes

Scientific Reports ◽

10.1038/s41598-019-50104-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Kornelia Schuetzenberger ◽

Martin Pfister ◽

Alina Messner ◽

Vanessa Froehlich ◽

Gerhard Garhoefer ◽

...

Keyword(s):

Optical Coherence Tomography ◽

High Frequency ◽

Ex Vivo ◽

Clinical Settings ◽

Optical Coherence ◽

High Frequency Ultrasound ◽

Skin Morphology ◽

Frequency Ultrasound ◽

Good Agreement

Abstract Optical coherence tomography (OCT) and high-frequency ultrasound (HFUS), two established imaging modalities in the field of dermatology, were evaluated and compared regarding their applicability for visualization of skin tissue morphology and quantification of murine intradermal structures. The accuracy and reproducibility of both methods were assessed ex vivo and in vivo using a standardized model for intradermal volumes based on injected soft tissue fillers. OCT revealed greater detail in skin morphology, allowing for detection of single layers due to the superior resolution. Volumetric data measured by OCT (7.9 ± 0.3 μl) and HFUS (7.7 ± 0.5 μl) were in good agreement and revealed a high accuracy when compared to the injected volume of 7.98 ± 0.8 µl. In vivo, OCT provided a higher precision (relative SD: 26% OCT vs. 42% HFUS) for the quantification of intradermal structures, whereas HFUS offered increased penetration depth enabling the visualization of deeper structures. A combination of both imaging technologies might be valuable for tumor assessments or other dermal pathologies in clinical settings.

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Delivery of human factor IX in mice by encapsulated recombinant myoblasts: a novel approach towards allogeneic gene therapy of hemophilia B

Blood ◽

10.1182/blood.v87.12.5095.bloodjournal87125095 ◽

1996 ◽

Vol 87 (12) ◽

pp. 5095-5103 ◽

Cited By ~ 114

Author(s):

G Hortelano ◽

A Al-Hendy ◽

FA Ofosu ◽

PL Chang

Keyword(s):

Gene Therapy ◽

Human Factor ◽

Ex Vivo ◽

Cost Effective ◽

Factor Ix ◽

Hemophilia B ◽

Therapy Strategy ◽

Human Factor Ix

A potentially cost-effective strategy for gene therapy of hemophilia B is to create universal factor IX-secreting cell lines suitable for implantation into different patients. To avoid graft rejection, the implanted cells are enclosed in alginate-polylysine-alginate microcapsules that are permeable to factor IX diffusion, but impermeable to the hosts' immune mediators. This nonautologous approach was assessed by implanting encapsulated mouse myoblasts secreting human factor IX into allogeneic mice. Human factor IX was detected in the mouse plasma for up to 14 days maximally at approximately 4 ng/mL. Antibodies to human factor IX were detected after 3 weeks at escalating levels, which were sustained throughout the entire experiment (213 days). The antibodies accelerated the clearance of human factor IX from the circulation of the implanted mice and inhibited the detection of human factor IX in the mice plasma in vitro. The encapsulated myoblasts retrieved periodically from the implanted mice up to 213 days postimplantation were viable and continued to secrete human factor IX ex vivo at undiminished rates, hence suggesting continued factor IX gene expression in vivo. Thus, this allogeneic gene therapy strategy represents a potentially feasible alternative to autologous approaches for the treatment of hemophilia B.

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Critical-care medicine and the acute-care laboratory

Clinical Chemistry ◽

10.1093/clinchem/36.8.1552 ◽

1990 ◽

Vol 36 (8) ◽

pp. 1552-1556 ◽

Cited By ~ 3

Author(s):

J R Hall

Keyword(s):

Critical Care ◽

Data Management ◽

Critically Ill ◽

Critically Ill Patients ◽

Ex Vivo ◽

Hospital Costs ◽

Cost Effective ◽

Critical Care Medicine ◽

Time Utilization

Abstract Critical-care medicine today is practiced by anesthesiologists, internists, pediatricians, and surgeons. Outcome from today's management of critically ill patients is very good, yet associated costs are very high. Over one-half of the hospital costs of critically ill patients emanates from the intensive-care unit (ICU), although the ICU stay accounts for less than 20% of their time in the hospital. Outside of the operating room, the ICU is the most expensive location for patient care in the hospital, and laboratory tests are the most expensive single item. Plans for cost containment should incorporate the following: more effective data management, education of practitioners about appropriateness and costs of tests, conversion from laboratory measurements to appropriate in vivo and ex vivo measurements, and real-time utilization assessment. To provide high-quality, cost-effective critical care in the future, laboratorians and clinicians must work together today to meet the challenges of technology, data management, and staff education.

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Smartphone microendoscopy for high resolution fluorescence imaging

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545816500462 ◽

2016 ◽

Vol 09 (05) ◽

pp. 1650046 ◽

Cited By ~ 9

Author(s):

Xiangqian Hong ◽

Vivek K. Nagarajan ◽

Dale H. Mugler ◽

Bing Yu

Keyword(s):

High Resolution ◽

Rural Areas ◽

Ex Vivo ◽

Cost Effective ◽

Internal Organs ◽

Middle Income ◽

Middle Income Countries ◽

The Past

High resolution optical endoscopes are increasingly used in diagnosis of various medical conditions of internal organs, such as the cervix and gastrointestinal (GI) tracts, but they are too expensive for use in resource-poor settings. On the other hand, smartphones with high resolution cameras and Internet access have become more affordable, enabling them to diffuse into most rural areas and developing countries in the past decade. In this paper, we describe a smartphone microendoscope that can take fluorescence images with a spatial resolution of 3.1 [Formula: see text]m. Images collected from ex vivo, in vitro and in vivo samples using the device are also presented. The compact and cost-effective smartphone microendoscope may be envisaged as a powerful tool for detecting pre-cancerous lesions of internal organs in low and middle-income countries (LMICs).

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