Jose Venegas | Harvard Medical School (original) (raw)

Papers by Jose Venegas

PubMed, Jun 1, 2006

Regional pulmonary perfusion and ventilation can be assessed by imaging, with positron emission t... more Regional pulmonary perfusion and ventilation can be assessed by imaging, with positron emission tomography (PET), the pulmonary kinetics of [13N]nitrogen (13N2). Because of its low solubility in blood and tissues, 13N2 infused intravenously in saline solution evolves into the alveolar airspace at first pass, where it accumulates in proportion to regional perfusion during a short apnea. In contrast, infused 13N2 is not retained in non-aerated regions, which do not exchange gas. Robust estimates of regional perfusion and shunt are obtained by modeling the pulmonary kinetics of 13N2 infused as a bolus during a short apnea. Regional ventilation is measured by modeling the washout of 13N2 after breathing is resumed. Regional gas content and dead space ventilation can be measured with inhalation of 13N2. Application of this novel functional imaging technique can further the understanding of the pathophysiology of a variety of pulmonary processes. This review briefly describes the methodological aspects of PET imaging of regional perfusion and ventilation and then focuses on insights in the pathophysiology of acute lung injury and asthma that have been gained by imaging the pulmonary kinetics of 13N2 with PET.

Omalizumab promotes clinical improvement in patients with allergic asthma, but its effect on pulm... more Omalizumab promotes clinical improvement in patients with allergic asthma, but its effect on pulmonary function is unclear. One possibility is that omalizumab improves asthma symptoms through effects on the regional distributions of ventilation, perfusion, and ventilation/perfusion matching, metrics which can be assessed with Nitrogen-13-saline Position Emission Tomography (PET). Four adults with moderate to severe uncontrolled allergic asthma underwent symptom assessment, spirometry and functional pulmonary imaging with Nitrogen-13-saline PET before and after 4-5 months of treatment with omalizumab. PET imaging was used to determine ventilation/ perfusion ratios, the heterogeneity (coefficient of variation, COV) of ventilation and perfusion, and lung regions with ventilation defects. There were no significant changes in spirometry values after omalizumab treatment, but there was a trend towards an improvement in symptom scores. There was little change in the matching of ventilation and perfusion. The COV of perfusion was similar before and after omalizumab treatment. The COV of ventilation was also similar before (0.57 (0.28)) and after (0.66 (0.13)) treatment, and it was similar to previously published values for healthy subjects. There was a non-significant trend towards an increase in the extent of ventilation defects after omalizumab treatment, from 5 (15)% to 12.8 (14.7)%. Treatment of moderate to severe uncontrolled allergic asthma with omalizumab did not result in a significant improvement in ventilation and perfusion metrics assessed with functional PET imaging. The normal COV of ventilation which was unaffected by treatment supports the hypothesis that omalizumab exerts its clinical effect on lung function during allergen exposure rather than in between exacerbations.

Journal of Aerosol Medicine and Pulmonary Drug Delivery, Aug 1, 2023

Barcelona respiratory network reviews, 2018

Obesity is a state of low-grade chronic systemic inflammation that induces a reduction of adipone... more Obesity is a state of low-grade chronic systemic inflammation that induces a reduction of adiponectin production with inhibition of the vasorelaxant properties of perivascular adipose tissue with underlying widespread endothelial dysfunction. This review concentrates on the main pulmonary and non-pulmonary determinants of gas exchange abnormalities, characterized by mild-to-moderate increased alveolar-arterial O 2 difference, with or without mild hypoxaemia, in non-smoking morbidly obese subjects without associated relevant co-morbidities, candidates to bariatric surgery, induced by ventilation-perfusion imbalance and increased intrapulmonary shunt, including the effects of 100% oxygen breathing and those induced by postural changes. Likewise, we review lung imaging abnormalities, more specifically lung tissue volume, and their interaction with gas exchange disturbances. Finally, we address the long-term beneficial effects of bariatric surgery on all these obesity-induced lung function and imaging defects. Overall, we present a compelling evidence of lung function and imaging abnormalities underlying systemic and pulmonary inflammation in morbidly obese candidates to bariatric surgery.

PLOS ONE, Jan 23, 2014

Background: Imaging studies have demonstrated that ventilation during bronchoconstriction in subj... more Background: Imaging studies have demonstrated that ventilation during bronchoconstriction in subjects with asthma is patchy with large ventilation defective areas (Vdefs). Based on a theoretical model, we postulated that during bronchoconstriction, as smooth muscle force activation increases, a patchy distribution of ventilation should emerge, even in the presence of minimal heterogeneity the lung. We therefore theorized that in normal lungs, Vdefs should also emerge in regions of the lung with reduced expansion. Objective: We studied 12 healthy subjects to evaluate whether Vdefs formed during bronchoconstriction, and compared their Vdefs with those observed in 9 subjects with mild asthma. Methods: Spirometry, low frequency (0.15 Hz) lung elastance and resistance, and regional ventilation by intravenous 13 NNsaline positron emission tomography were measured before and after a challenge with nebulized methacholine. Vdefs were defined as regions with elevated residual 13 NN after a period of washout. The average location, ventilation, volume, and fractional gas content of the Vdefs, relative to those of the rest of the lung, were calculated for both groups. Results: Consistent with the predictions of the theoretical model, both healthy subjects and those with asthma developed Vdefs. These Vdefs tended to form in regions that, at baseline, had a lower degree of lung inflation and, in healthy subjects, tended to occur in more dependent locations than in subjects with asthma. Conclusion: The formation of Vdefs is determined by the state of inflation prior to bronchoconstriction.

Anesthesiology, Sep 1, 2002

American Society of Anesthesiologists. Contact ASA. | Advertising Information. Reach more than 44... more American Society of Anesthesiologists. Contact ASA. | Advertising Information. Reach more than 44,000 ASA members through a variety of marketing channels. ...

The Journal of Nuclear Medicine, Oct 6, 2014

PET with 18 F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neu... more PET with 18 F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neutrophilic inflammation. This study aimed at determining during early acute lung injury whether local 18 F-FDG phosphorylation rate and volume of distribution were sensitive to the initial regional inflammatory response and whether they depended on the mechanism of injury: endotoxemia and surfactant depletion. Methods: Twelve sheep underwent homogeneous unilateral surfactant depletion (alveolar lavage) and were mechanically ventilated for 4 h (positive end-expiratory pressure, 10 cm H 2 O; plateau pressure, 30 cm H 2 O) while receiving intravenous endotoxin (lipopolysaccharide-positive [LPS1] group; n 5 6) or not (lipopolysaccharide-negative group; n 5 6). 18 F-FDG PET emission scans were then acquired. 18 F-FDG phosphorylation rate and distribution volume were calculated with a 4-compartment model. Lung tissue expression of inflammatory cytokines was measured using real-time quantitative reverse transcription polymerase chain reaction. Results: 18 F-FDG uptake increased in LPS1 (P 5 0.012) and in surfactant-depleted sheep (P , 0.001). These increases were topographically heterogeneous, predominantly in dependent lung regions, and without interaction between alveolar lavage and LPS. The increase of 18 F-FDG uptake in the LPS1 group was related both to increases in the 18 F-FDG phosphorylation rate (P , 0.05) and to distribution volume (P , 0.01). 18 F-FDG distribution volume increased with infiltrating neutrophils (P , 0.001) and phosphorylation rate with the regional expression of IL-1β (P 5 0.026), IL-8 (P 5 0.011), and IL-10 (P 5 0.023). Conclusion: Noninvasive 18 F-FDG PET-derived parameters represent histologic and gene expression markers of early lung injury. Pulmonary metabolism assessed with 18 F-FDG PET depends on the mechanism of injury and appears to be additive for endotoxemia and surfactant depletion. 18 F-FDG PET may be a valuable imaging biomarker of early lung injury.

Critical Care Medicine, Jul 1, 2014

Objective-Regional tidal lung strain may trigger local inflammation during mechanical ventilation... more Objective-Regional tidal lung strain may trigger local inflammation during mechanical ventilation, particularly when additional inflammatory stimuli are present. However, it is unclear whether inflammation develops proportionally to tidal strain or only above a threshold. We aimed to: (1) assess the relationship between regional tidal strain and local inflammation in vivo during the early stages of lung injury in lungs with regional aeration heterogeneity comparable to that of humans; and (2) determine how this strain-inflammation relationship is affected by endotoxemia. Design-Interventional animal study. Setting-Experimental laboratory and positron emission tomography (PET) facility. Subjects-Eighteen 2-4-month-old sheep. Interventions-Three groups of sheep (n=6) were mechanically ventilated to the same plateau pressure (30-32 cmH 2 O) with High-Strain (V T =18.2±6.5 ml/kg, PEEP=0), High-Strain plus intravenous lipopolysaccharide (LPS) (V T =18.4±4.2 ml/kg, PEEP=0), or Low-Strain plus LPS (V T =8.1±0.2 ml/kg, PEEP=17±3 cmH 2 O). At baseline, we acquired respiratory-gated PET scans

The ability to determine the condition of injured lungs is crucial in pulmonary medicine. Althoug... more The ability to determine the condition of injured lungs is crucial in pulmonary medicine. Although current available methodologies are able to aid in these decisions, most are invasive in nature, time consuming, and cannot be combined on the same patient for simultaneous measurements of all the variables relevant to pulmonary function. With appropriate physiological models, Positron Emission Tomography ( PET) provides a unique opportunity to non-invasively and accurately quantify the required variables needed to obtain an unbiased view of the injured lung condition. This thesis deals with novel methodologies to produce and analyze PET images of perfusion (0), alveoli ventilation (VA), VA /Q ratio, and intrapulmonary blood shunt on the same subject non-invasively. These methodologies represent a significant advancement over existing procedures in the topographic determination of injured lung condition. The methodologies and models were implemented in studies to accurately determine l...

L'invention concerne l'ecoulement lateral entre des segments de poumon adjacents qui est ... more L'invention concerne l'ecoulement lateral entre des segments de poumon adjacents qui est occlus en bloquant les canaux d'ecoulement collateral avec des particules. Un ecoulement gazeux est etabli a partir d'un segment de poumon a travers les canaux d'ecoulement dans un septum fibreux intermediaire, et a l'exterieur a travers le segment de poumon adjacent. Les particules entrainees dans l'ecoulement gazeux viennent se loger dans les canaux d'ecoulement collateral pour finalement bloquer l'ecoulement.

Running head: Tracer kinetics model of pulmonary function

Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology

The coefficient of variation (CoV) is frequently used to describe functional or structural hetero... more The coefficient of variation (CoV) is frequently used to describe functional or structural heterogeneity but is overestimated by the contribution of noise from the measurement method. We evaluated a method to estimate a noise-corrected heterogeneity. It delivers results with a narrow confidence interval. That method has been used to estimate the heterogeneity of pulmonary blood flow in humans as well

$Research paper thumbnail of application to PET images of pulmonary blood flow Low-pass filtering, a new method of fractal analysis$

medRxiv (Cold Spring Harbor Laboratory), Aug 17, 2022

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.