Proposed Mechanism of Pulmonary Gas Trapping (Pgt) Following Intravenous Perfluorocarbon Emulsion Administration

Schutt, Ernest G.; Barber, P A; Fields, Tony; Flaim, Stephen F.; Horodniak, J.; Keipert, Peter E.; Kinner, R.; Kornbrust, L.; Leakakos, Tina; Pelura, Timothy J.; Weers, Jeffry G.; Houmes, Robert Jan; Lachmann, B.

doi:10.3109/10731199409138817

Cited by 10 publications

(11 citation statements)

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“…In the case of fluorocarbon blood substitutes, the boiling point range was 120–180°C whereas the boiling point of PFP is 29°C. Though HNCL was not previously observed in canines following the administration of fluorocarbon blood substitutes (Schutt et al 1994), it may be likely that the elevated vapor pressure of PFP and subsequent gas-trapping could have caused the observed respiratory distress, when approximately 3×10 9 droplets/kg were injected IV.…”

Section: Discussionmentioning

confidence: 78%

“…Others have found that after the administration of fluorocarbon-based artificial blood substitutes, the likelihood of hyperinflated non-collapsible lungs (HNCL) (Clark et al 1992; Flaim 1994) attributed to pulmonary gas trapping (Schutt et al 1994) increased as the boiling point of the fluorocarbon decreased. This is due to the inverse relation between boiling point and vapor pressure.…”

Section: Discussionmentioning

confidence: 99%

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Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

Zhang

Fabiilli

Haworth

et al. 2010

Ultrasound in Medicine & Biology

123

116

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Acoustic droplet vaporization (ADV) shows promise for spatially and temporally targeted tissue occlusion. In this study, substantial tissue occlusion was achieved in operatively exposed and transcutaneous canine kidneys by generating ADV gas bubbles in the renal arteries or segmental arteries. Fifteen canines were anesthetized, among which 10 underwent laparotomy to externalize the left kidney and 5 were undisturbed for transcutaneous ADV. The microbubbles were generated by phase conversion of perfluoropentane droplets encapsulated in albumin or lipid shells in the blood. A 3.5 MHz single-element therapy transducer was aligned with an imaging array in a water tank with direct access to the renal artery or a segmental artery. In vivo color flow and spectral Doppler imaging were used to identify the target arteries. Tone bursts of 1 kHz pulse repetition frequency with 0.25% duty cycle vaporized the droplets during bolus passage. Both intracardiac (IC) and intravenous (IV) injections repeatedly produced ADV in chosen arteries in externalized kidneys, as seen by B-mode imaging. Concurrent with this in two cases was the detection by pulse wave Doppler of blood flow reversal, along with a narrowing of the waveform. Localized cortex occlusion was achieved with 87% regional flow reduction in one case using IC injections. Vaporization from IV injections resulted in a substantial echogenicity increase with an average half-life of 8 minutes per droplet dose. Gas bubbles sufficient to produce some shadowing were generated by transcutaneous vaporization of intra renal artery or IV administered droplets, with a tissue path up to 5.5 cm.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

Zhang

Fabiilli

Haworth

et al. 2010

Ultrasound in Medicine & Biology

123

116

View full text Add to dashboard Cite

show abstract

“…The stable vital signs of the canine during the experiment and the normal-looking lungs observed after the experiment implied minimal acute, unintended, bioeffects from the injected perfluoropentane droplets (36, 48, 49). However, a more thorough examination of potential bioeffects is warranted.…”

Section: Discussionmentioning

confidence: 93%

Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound

Zhang¹,

Fabiilli²,

Haworth³

et al. 2011

Academic Radiology

105

106

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Rationale and Objectives Acoustic droplet vaporization (ADV) shows promise for spatial control and acceleration of thermal lesion production. Our hypothesis was that microbubbles generated by ADV could enhance high intensity focused ultrasound (HIFU) thermal ablation by controlling and increasing local energy absorption. Materials and Methods Thermal lesions were produced in tissue-mimicking phantoms using focused ultrasound (1.44 MHz) with a focal intensity of 4000 W·cm-2 in degassed water at 37°C. The average lesion volume was measured by visible change in optical opacity and by T2-weighted MRI. In addition, in vivo HIFU lesions were generated in a canine liver before and after an intravenous injection of droplets with a similar acoustic setup. Results Thermal lesions were seven-fold larger in phantoms containing droplets (3×105 droplets/mL) compared to phantoms without droplets. The mean lesion volume with a 2 s HIFU exposure in droplet-containing phantoms was comparable to that made by a 5 s exposure in phantoms without droplets. In the in vivo study, the average lesion volumes without and with droplets were 0.017 ± 0.006 cm3 (n = 4, 5 s exposure) and 0.265 ± 0.005 cm3 (n = 3, 5 s exposure), respectively – a factor of 15 difference. The shape of ADV bubbles imaged with B-mode ultrasound was very similar to the actual lesion shape as measured optically and by MRI. Conclusion ADV bubbles may facilitate clinical HIFU ablation by reducing treatment time or requisite in situ total acoustic power, and provide ultrasonic imaging feedback of the thermal therapy.

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“…diagnostic vs therapeutic) and incorporated imaging marker (e.g. 19 F for MRI or 18 F for PET), these modalities enable the visualization of the PFC phase, surfactant or therapeutic payload. Small animal PET (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…For example, lung retention of microbubbles within the pulmonary microvasculature is a size‐dependent phenomenon . The formulation of transpulmonary, micron‐sized emulsions can minimize certain types of PFC‐related bioeffects . Additionally, the pharmacokinetics of sonosensitive PFC particles are directly related to the time window between vascular administration of the particles and the application of ultrasound to activate the particles.…”

Section: Introductionmentioning

confidence: 99%

Assessment of the biodistribution of an [¹⁸F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats

Fabiilli

Piert

Koeppe

et al. 2013

Contrast Media & Molecular

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Perfluorocarbon (PFC) double emulsions loaded with a water-soluble, therapeutic agent can be triggered by ultrasound in a process known as acoustic droplet vaporization (ADV). Elucidating the stability and biodistribution of these sonosensitive vehicles and encapsulated agents are critical in developing targeted drug delivery strategies using ultrasound. [18F]fluorodeoxyglucose (FDG) was encapsulated in a PFC double emulsion and the in vitro diffusion of FDG was assessed using a Franz diffusion cell. Using dynamic micro positron emission tomography (micro-PET) and direct tissue sampling, the biodistribution of FDG administered as a solution (i.e. non-emulsified) or as an emulsion was studied in Fisher 344 rats (n = 6) bearing subcutaneous 9L gliosarcoma. Standardized uptake values (SUVs) and area under the curve of the SUV (AUCSUV) of FDG were calculated for various tissues. The FDG flux from the emulsion decreased by up to a factor of 6.9 compared to the FDG solution. FDG uptake, calculated from the AUCSUV, decreased by 36% and 44% for brain and tumor, respectively, when comparing FDG solution versus FDG emulsion (p < 0.01). Decreases in AUCSUV in highly metabolic tissues such as brain and tumor demonstrated retention of FDG within the double emulsion. No statistically significant differences in lung AUCSUV were observed, suggesting minimal accumulation of the emulsion in the pulmonary capillary bed. The liver AUCSUV increased by 356% for the FDG emulsion, thus indicating significant hepatic retention of the emulsion.

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Proposed Mechanism of Pulmonary Gas Trapping (Pgt) Following Intravenous Perfluorocarbon Emulsion Administration

Abstract: Experimental observations are consistent with the proposed theory of perfluorocarbon-related gas osmosis through micro-bubbles that prevent complete lung collapse as observed upon opening the thoracic cavity of test animals.

Cited by 10 publications

References 1 publication

Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound

Assessment of the biodistribution of an [¹⁸F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats

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Proposed Mechanism of Pulmonary Gas Trapping (Pgt) Following Intravenous Perfluorocarbon Emulsion Administration

Abstract: Experimental observations are consistent with the proposed theory of perfluorocarbon-related gas osmosis through micro-bubbles that prevent complete lung collapse as observed upon opening the thoracic cavity of test animals.

Cited by 10 publications

References 1 publication

Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound

Assessment of the biodistribution of an [18F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats

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Product

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Assessment of the biodistribution of an [¹⁸F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats