Lung Tissue Volume Research Articles

The dependence of optimal fractionation schemes on the spatial dose distribution

We consider the fractionation problem in radiation therapy. Tumor sites in which the dose-limiting organ at risk (OAR) receives a substantially lower dose than the tumor, bear potential for hypofractionation even if the α/β-ratio of the tumor is larger than the α/β-ratio of the OAR. In this work, we analyze the interdependence of the optimal fractionation scheme and the spatial dose distribution in the OAR. In particular, we derive a criterion under which a hypofractionation regimen is indicated for both a parallel and a serial OAR. The approach is based on the concept of the biologically effective dose (BED). For a hypothetical homogeneously irradiated OAR, it has been shown that hypofractionation is suggested by the BED model if the α/β-ratio of the OAR is larger than α/β-ratio of the tumor times the sparing factor, i.e. the ratio of the dose received by the tumor and the OAR. In this work, we generalize this result to inhomogeneous dose distributions in the OAR. For a parallel OAR, we determine the optimal fractionation scheme by minimizing the integral BED in the OAR for a fixed BED in the tumor. For a serial structure, we minimize the maximum BED in the OAR. This leads to analytical expressions for an effective sparing factor for the OAR, which provides a criterion for hypofractionation. The implications of the model are discussed for lung tumor treatments. It is shown that the model supports hypofractionation for small tumors treated with rotation therapy, i.e. highly conformal techniques where a large volume of lung tissue is exposed to low but nonzero dose. For larger tumors, the model suggests hyperfractionation. We further discuss several non-intuitive interdependencies between optimal fractionation and the spatial dose distribution. For instance, lowering the dose in the lung via proton therapy does not necessarily provide a biological rationale for hypofractionation.

Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

BackgroundPrevious studies have demonstrated an important role for beta-2 adrenergic receptors (β2AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β2AR density on lymphocytes and indices of lung water in healthy humans exposed to ∼17h of hypoxia (FIO2=12.5% in a hypoxia tent). MethodsThirteen adults (mean±SEM; age=31±3 years, BMI=24±1kg/m2, VO2 Peak=40±2 ml/kg/min) participated. Pulmonary function, CT derived lung tissue volume (Vtis-tissue, blood and water), lung diffusing capacity for carbon monoxide (DCO) and nitric oxide (DNO), alveolar-capillary conductance (DM), pulmonary capillary blood volume (Vc) and lung water (CT Vtis−Vc) were assessed before and after ∼17h normobaric hypoxia (FIO2=12.5%). β2AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (SaO2), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed. ResultsAfter 17h hypoxia, SaO2 decreased from 97±1 (normoxia) to 82±4% and RVSP increased from 14±3 (normoxia) to 29±2mmHg (p<0.05) with little change in Q or BP. Vc and DM both increased with hypoxia with a small increase in DM/Vc ratio (p>0.05). CT Vtis decreased and lung water was estimated to decline 7±13%, respectively. β2AR density averaged 1497±187 receptors/lymphocyte and increased 21±34% with hypoxia (range −31 to +86%). The post-hypoxia increase in β2AR density was significantly related to the reduction in lung water (r=−0.64, p<0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water. ConclusionsLung water decreases with 17h normobaric hypoxia are associated with changes in beta adrenergic receptor density on lymphocytes in healthy adults.

The effect of β2 adrenergic‐receptor stimulation on lung fluid balance in heart failure

BackgroundIncreased pulmonary capillary pressure and a possible desensitization of lung β2 adrenergic receptors (β2AR) involved in fluid removal mechanisms may increase extravascular lung water (ELW) in stable heart failure (HF) patients. Whether these patients exhibit increased ELW remains controversial.PurposeTo determine if HF patients have elevated ELW versus controls (CTL) and if acute β2AR agonist inhalation stimulates fluid removal.Methods/Results14 stable HF patients and 19 healthy age/gender matched CTL were studied. Lung tissue volume (Vtis) (includes tissue, blood and water) and pulmonary capillary blood volume (Vc) were assessed pre and post nebulized albuterol via CT and rebreathe, respectively. ELW was derived as Vtis – Vc. Pre albuterol, ELW was greater in HF vs. CTL (861±241 vs. 739±143 ml, P&lt;0.01), with no difference in Vtis (938±246 vs. 830±151 ml, P=0.08). Albuterol decreased Vtis (–4±2%, P=0.02) but did not change ELW (739±143 vs. 724±132 ml) (P&gt;0.05) in CTL. In HF, albuterol decreased both Vtis (–5±3%) and ELW (– 4±2%) (P&lt;0.05). There was a negative relationship between baseline values and the pre to post albuterol change for Vtis (r2=0.38) and ELW (r2=0.42) (P&lt;0.01) in HF.ConclusionLung fluid is elevated in stable HF patients relative to healthy subjects. Stimulation of β2ARs appears to enhance fluid removal in HF, especially in patients with elevated lung water at rest.

Tracking regional tissue volume and function change in lung using image registration.

We have previously demonstrated the 24-hour redistribution and reabsorption of bronchoalveolar lavage (BAL) fluid delivered to the lung during a bronchoscopic procedure in normal volunteers. In this work we utilize image-matching procedures to correlate fluid redistribution and reabsorption to changes in regional lung function. Lung CT datasets from six human subjects were used in this study. Each subject was scanned at four time points before and after BAL procedure. Image registration was performed to align images at different time points and different inflation levels. The resulting dense displacement fields were utilized to track tissue volume changes and reveal deformation patterns of local parenchymal tissue quantitatively. The registration accuracy was assessed by measuring landmark matching errors, which were on the order of 1 mm. The results show that quantitative-assessed fluid volume agreed well with bronchoscopist-reported unretrieved BAL volume in the whole lungs (squared linear correlation coefficient was 0.81). The average difference of lung tissue volume at baseline and after 24 hours was around 2%, which indicates that BAL fluid in the lungs was almost absorbed after 24 hours. Regional lung-function changes correlated with the presence of BAL fluid, and regional function returned to baseline as the fluid was reabsorbed.

Multiphase-computed tomography-based target volume definition in conventional fractionated radiotherapy of lung tumors: Dosimetric and reliable comparison with the technique using addition of generic margins

The aim of the present study was to compare radiotherapeutic plans based on internal target volume determined by between multiphase computed tomography and addition of a generic margin in lung tumors and to evaluate the reliability of ITV determined by multiphase computed tomography during conventional fractionated radiotherapy. The radiotherapeutic plans based on internal target volume determined by between multiphase computed tomography and addition of a generic margin in 10 patients with lung tumors were applied. The difference of two planning target volumes (PTV) and irradiated dose and volume of normal lung tissue were compared. Weekly new targets were delineated on repeated computed tomography scans, and weekly dose coverage of clinical target volume under two different treatment plans was evaluated. For all patients, PTV3CT volume based on multiphase computed tomography was significantly smaller than that of PTVcon based on addition of a generic margin (t = 6.831, P <0.001). The volume receiving more than 20 Gy in Plan3CT and Plancon was 16.7 ± 5.2% and 20.0 ± 5.2% (t = 7.565, P <0.001), the volume receiving more than 5 Gy was 36.6 ± 7.2% and 42.7 ± 6.4% (t = 7.459, P <0.001), and mean lung dose was 1037.5 ± 275.0 cGy and 1246.8 ± 271.0 cGy (t = 8.078, P <0.001), respectively. Both Plan3CT and Plancon provided a satisfactory clinical target volume coverage weekly during conventional fractionated radiotherapy for 6-7 weeks, and the ratio of the volume receiving the prescription dose was 1.03 ± 0.02 and 1.04 ± 0.02, respectively. The radiotherapeutic plan based on internal target volume determined by multiphase computed tomography can ensure weekly target coverage during conventional fractionated radiotherapy in lung tumors, and it is better than the plan based on the addition of generic internal target volume, which can effectively reduce normal lung tissue irradiation.

Subclinical Lung Disease, Macrocytosis, and Premature Graying in Kindreds With Telomerase (TERT) Mutations

Mutations in the human gene encoding the protein component of telomerase (TERT) are the most common genetic defect in patients with familial idiopathic pulmonary fibrosis (IPF). The subclinical phenotypes of asymptomatic members of these families have not been evaluated with respect to TERT mutation status or telomere length. We measured a variety of pulmonary, blood, skin, and bone parameters for 20 subjects with heterozygous TERT mutations (carriers) and 20 family members who had not inherited a TERT mutation (noncarriers) to identify the spectrum of phenotypes associated with mutations in this gene. The two groups were matched for sex, age, and cigarette smoking. Three TERT mutation carriers had IPF (IPF carriers). The rest of the carriers were apparently healthy (asymptomatic carriers) and were compared with the noncarriers. Asymptomatic carriers exhibited significantly lower diffusing capacity of lung for carbon monoxide (Dlco), impaired recruitment of Dlco with exercise, radiographic signs of lung fibrosis, and increased fractional lung tissue volume quantified by high-resolution chest CT scan than noncarriers. RBC and platelet counts were significantly lower, and the mean corpuscular volume and mean corpuscular hemoglobin concentration were significantly higher in carriers than in noncarriers. Carriers reported significantly earlier graying of hair than noncarriers. TERT mutation status is more accurately predicted by short telomere lengths than any of these measured phenotypes. TERT mutation carriers exhibit early preclinical signs of lung fibrosis, bone marrow dysfunction, and premature graying. These clinical features and short telomere lengths characterize patients with germline TERT mutations.

A new method to deliver supraclavicular radiation in breast radiotherapy for lung sparing

Due to the angulation of the breast board used for tangential breast irradiation, additional normal lung tissues are included in the supraclavicular field. This work investigates a method to reduce the lung volume and dose delivered during supraclavicular irradiation for breast cancer. Ten patients included for this retrospective study received chest wall and supraclavicular irradiation following radical surgery or breast‐conserving surgery. Three‐dimensional conformal radiation therapy plans were generated using the CMS XiO treatment planning system. The clinical target volume (CTV) of the supraclavicular irradiation is defined as the subcutaneous tissues from 0.5 cm under the anterior skin surface to a 3 cm depth. Only the ipsilateral lung is defined as the organ at risk. In the new method, the couch is rotated 90° and the supraclavicular field is tilted to maintain a normal incident angle to the breast board rather than the couch surface to spare more normal lung tissues. The absolute volume of the ipsilateral lung irradiated, and the volumes of lung tissues receiving 5 Gy and 20 Gy (V5 and V20) are analyzed. The new method can reduce the lung volume irradiated by the supraclavicular field significantly. For the ten patients investigated, only 5.3% of the ipsilateral lung is irradiated with the new method, while 14.9% of the ipsilateral lung is irradiated using the conventional method. Compared with the conventional method, the new method reduces V5 by 53.6% and V20 by 59.0%. Our new method does not alter the patient positioning for breast treatment but rotates the couch to deliver a tilted supraclavicular field to maintain adequate CTV coverage and spare more normal lung tissues. The results of this study demonstrated that our new method is effective, and that the reduction of normal lung tissue volume in the field is significant.PACS number: 87.55.D‐

Estimation of inhomogenity correction factors for a Co-60 beam using Monte Carlo simulation

The aim was to obtain inhomogenity correction factors (ICFs) for lung tissue inhomogenity for a Co-60 teletherapy beam using Monte Carlo simulation and to compare them with factors obtained from a commercially available treatment planning system. The Monte Carlo simulation code of EGSnrc is used for the depth dose calculations. Two clinical like situations were simulated-dose calculation point beyond the lung tissue volume and dose calculation point within the lung tissue volume. The variation of ICF with lung thicknesses and positions was studied. ICF values were obtained for the similar situations from a commercially available treatment planning system, Theraplan Plus. Percentage depth dose data obtained from Monte Carlo simulation is well matching with the published measurement data. ICFs for lung tissue inhomogenity calculated using the Monte Carlo code are in good agreement with Theraplan Plus TPS values for small inhomogenity thicknesses. These results can be used for the verification of TPS calculation or manual treatment time calculation.

A treatment planning study of the potential of geometrical tracking for intensity modulated proton therapy of lung cancer

Background. Proton therapy of lung cancer holds the potential for a reduction of the volume of irradiated normal lung tissue. In this work we investigate the robustness of intensity modulated proton therapy (IMPT) plans to motion, and evaluate a geometrical tumour tracking method to compensate for tumour motion. Material and methods. Seven patients with a nine targets with 4DCT scans were selected. IMPT plans were made on the midventilation phase using a 3-field technique. The plans were transferred and calculated on the remaining nine phases of the 4DCT, and the combined dose distribution was summed using deformable image registration (DIR). An additional set of plans were made in which the proton beam was simply geometrically shifted to the centre of the gross tumour volume (GTV), i.e. simulating tracking of the tumour motion but without on-line adjustment of the proton energies. A possible interplay effect between the dynamics of the spot scanning delivery and the tumour motion has not been considered in this work. Results. Around 97–100% of the GTV was covered by 95% of the prescribed dose (V95) for a tumour displacement of less than about 1 cm with a static beam. For the remaining three of nine targets with a larger motion the tracking method studied provided a marked improvement over static beam; raising the GTV V95 from 95 to 100%, 82 to 98% and 51 to 97%, respectively. Conclusion. The possibility of performing DIR and summing the dose on the 4DCT data set was shown to be feasible. The fairly simplistic tracking method suggested here resulted in a marked improvement in GTV coverage for tumours with large intra-fractional motion (>1 cm displacement), indicating that on-line adjustment of the proton energies may be redundant.

Radiographic lung density assessed by computed tomography is associated with extravascular lung water content

We hypothesized that in acute lung injury (ALI), the volume of pulmonary tissue with aqueous density, as determined by spiral computed tomography (CT), is associated with extravascular lung water content. Our aim was to compare tissue volume index, as assessed by CT, before and after oleic acid-induced ALI, with extravascular lung water indexes (EVLWI), determined with single transpulmonary thermodilution (EVLWI(STD)), thermal-dye dilution (EVLWI(TDD)), and postmortem gravimetry (EVLWI(G)). Seven instrumented sheep received an intravenous infusion of oleic acid 0.08 ml/kg (OA group) and four animals had vehicle only (Control group). The day before, and immediately after the experiment, sheep were anesthetized to undergo quantitative CT examinations during a short breath hold. Hemodynamics, oxygenation, EVLWI(STD), and EVLW(TDD) were registered. Linear regression analysis was used to assess the relationships between EVLWI(STD), EVLW(TDD), EVLWI(G), and lung tissue volume index (TVI(CT)) determined with CT. In the OA group, total lung volume increased compared with Controls. Poorly and non-aerated lung volumes increased a 3.6- and 4.9-fold, respectively, and TVI(CT) almost doubled. EVLWI(STD), EVLWI(TDD), and TVI(CT) were associated significantly with EVLWI(G) (r=0.85, 0.90, and 0.88, respectively; P<0.001). TVI(CT) deviated from the reference EVLWI(G) values to the greatest extent with a mean bias +/- 2SD of 4.0 +/- 6.0 ml/kg. In ovine oleic acid-induced ALI, lung tissue volume, as assessed by quantitative CT, is in close agreement with EVLWI, as determined by indicator dilution methods and postmortem gravimetry, but overestimates lung fluid content.

Ultra‐short echo time (UTE) MR imaging of the lung: Comparison between normal and emphysematous lungs in mutant mice

To investigate the utility of ultra-short echo time (UTE) sequence as pulmonary MRI to detect non-uniform disruption of lung architecture that is typical of emphysema. MRI of the lungs was conducted with a three-dimensional UTE sequence in transgenic mice with severe emphysema and their wild-type littermates in a 3 Tesla clinical MR system. Measurements of the signal intensity (SI) and transverse relaxation time (T2*) of the lung parenchyma were performed with various echo times (TEs) ranging from 100 micros to 2 ms. Much higher SI of the lung parenchyma was observed at an UTE of 100 micros compared with longer TEs. The emphysematous lungs had reduced SIs and T2* than the controls, in particular at end-expiratory phase. The results suggested that both SI and T2* in lung parenchyma measured with the method represent fractional volume of lung tissue. The UTE imaging provided MR signal from the lung parenchyma. Moreover, the UTE sequence was sensitive to emphysematous changes and may provide a direct assessment of lung parenchyma. UTE imaging has the potential to assist detection of localized pathological destruction of lung tissue architecture in emphysema.

Evaluation of lung inflammation induced by intratracheal administration of LPS in mice: comparison between MRI and histology

To study the in vivo effect of intratracheal administration of lipopolysaccharide (LPS) in mice by magnetic resonance imaging (MRI) and to investigate the correlation with ex vivo histological evaluation of lung inflammation and oedema. LPS (or phosphate buffered saline) was administered intratracheally to thirty male Balb/C mice at a concentration of 0.3 mg/ml in a total volume of 100 microl. Animals were divided into fifteen LPS-treated and fifteen control mice. MR images were acquired 24 h after challenge in freely breathing animals with standard ECG-gated Gradient-Echo (GRE) sequences and, in a limited number of animals, with ECG-gated Ultrashort-echo time (UTE) sequences. After MRI, animals were sacrificed, and lungs were fixed and processed for histological analysis of the total volume of healthy lung tissue. GRE images revealed the presence of high intensity signal in lungs of LPS-treated mice that was attributable to oedema caused by alveolar inflammation. In histological slices, regions of alterations in the normal alveolar microstructure were observed that could account for MRI findings. A good correlation was observed between the volumes of lesioned tissue measured by MRI and by histology. The volume of the lesion detected by GRE sequences was lower than the volume detected by UTE sequences. The effect of intratracheal administration of LPS in mice was investigated by MRI and histology. A good correlation was observed between GRE-MRI and histological findings. MR images obtained with UTE sequences appear to be more sensitive to the presence of lesions than those obtained by standard GRE acquisitions.

Ventilation and Oxygen: Dose-Related Effects of Oxygen on Ventilation-Induced Lung Injury

Preterm infants are at high risk of developing ventilator-induced lung injury. We have used an animal model of in utero ventilation (IUV) to investigate the separate effects of ventilation and acute oxygen exposure on the very immature lung. Fetal sheep were ventilated in utero at 110 d gestation for 6 h with 100, 21, or 0% (100% nitrogen) oxygen (n = 5 each) and survived in utero, without further ventilation, until tissue collection at 118 d. Nonventilated 110 d and 118 d fetuses were used as controls. All IUV exposed fetuses had reduced secondary septal crest densities and increased elastin staining irrespective of the inspired oxygen concentration. IUV with 100% and 21% oxygen, but not 100% nitrogen, increased lung tissue volumes and myofibroblast differentiation and apoptosis within the distal lung parenchyma in a dose-dependent manner. This study shows that IUV without oxygen can reduce alveolarization, whereas ventilation with oxygen (6 h), even at levels found in air (21%), increases distal lung tissue volumes, elastin deposition, myofibroblast differentiation, and apoptosis.

CT Density in Lung Cancer Patients After Radiotherapy Sensitized by Metoclopramide

To investigate the lung tissue response measured with computed tomography (CT) after radiotherapy (RT) combined with metoclopramide. Patients with non-small cell lung cancer (tumor stage IIIA and IIIB), included in a multicenter, randomized phase III trial investigating the use of metoclopramide as a radiosensitizing agent, were examined with repetitive post-RT CT scans. The analysis comprised data up to 100 days after RT for a subgroup of 16 patients treated with a total dose of 60 Gy given in 1.82 Gy per fraction. Large radiation doses to subvolumes were associated with denser lung tissue measured with CT (p < 0.001). Opposed to this finding, the volume of lung tissue irradiated with significant doses (V(40Gy)) was negatively correlated with the average increase in lung tissue density (p = 0.003). Patients randomized to metoclopramide injections also experienced less increase in lung tissue density (p = 0.01). There was an increase in the density of irradiated lung tissue with radiation dose and time after RT. Metoclopramide and significant radiation doses to larger lung volumes (V(40Gy)) seemed to protect against fibrosis development.

Quantitative Assessment of Irradiated Lung Volume and Lung Mass in Breast Cancer Patients Treated with Tangential Fields in Combination with Deep Inspiration Breath Hold (DIBH)

Comparison of the amount of irradiated lung tissue volume and mass in patients with breast cancer treated with an optimized tangential-field technique with and without a deep inspiration breath-hold (DIBH) technique and its impact on the normal-tissue complication probability (NTCP). Computed tomography datasets of 60 patients in normal breathing (NB) and subsequently in DIBH were compared. With a Real-Time Position Management Respiratory Gating System (RPM), anteroposterior movement of the chest wall was monitored and a lower and upper threshold were defined. Ipsilateral lung and a restricted tangential region of the lung were delineated and the mean and maximum doses calculated. Irradiated lung tissue mass was computed based on density values. NTCP for lung was calculated using a modified Lyman-Kutcher-Burman (LKB) model. Mean dose to the ipsilateral lung in DIBH versus NB was significantly reduced by 15%. Mean lung mass calculation in the restricted area receiving ≤ 20 Gy (M(20)) was reduced by 17% in DIBH but associated with an increase in volume. NTCP showed an improvement in DIBH of 20%. The correlation of individual breathing amplitude with NTCP proved to be independent. The delineation of a restricted area provides the lung mass calculation in patients treated with tangential fields. DIBH reduces ipsilateral lung dose by inflation so that less tissue remains in the irradiated region and its efficiency is supported by a decrease of NTCP.

Low-Intensity Swimming Training Partially Inhibits Lipopolysaccharide-Induced Acute Lung Injury

Aerobic exercise decreases pulmonary inflammation and remodeling in experimental models of allergic asthma. However, the effects of aerobic exercise on pulmonary inflammation of nonallergic origin, such as in experimental models of acute lung injury induced by lipopolysaccharide (LPS), have not been evaluated. The present study evaluated the effects of aerobic exercise in a model of LPS-induced acute lung injury. BALB/c mice were divided into four groups: Control, Aerobic Exercise, LPS, and Aerobic Exercise + LPS. Swimming tests were conducted at baseline and at 3 and 6 wk. Low-intensity swimming training was performed for 6 wk, four times per week, 60 min per session. Intranasal LPS (1 mg x kg(-1) (60 microg per mouse)) was instilled 24 h after the last swimming physical test in the LPS and Aerobic Exercise + LPS mice, and the animals were studied 24 h after LPS instillation. Exhaled nitric oxide, respiratory mechanics, total and differential cell counts in bronchoalveolar lavage, and lung parenchymal inflammation and remodeling were evaluated. LPS instillation resulted in increased levels of exhaled nitric oxide (P < 0.001), higher numbers of neutrophils in the bronchoalveolar lavage (P < 0.001) and in the lung parenchyma (P < 0.001), and decreased lung tissue resistance (P < 0.05) and volume proportion of elastic fibers (P < 0.01) compared with the Control group. Swim training in LPS-instilled animals resulted in significantly lower exhaled nitric oxide levels (P < 0.001) and fewer neutrophils in the bronchoalveolar lavage (P < 0.001) and the lung parenchyma (P < 0.01) compared with the LPS group. These results suggest that low-intensity swimming training inhibits lung neutrophilic inflammation, but not remodeling and impaired lung mechanics, in a model of LPS-induced acute lung injury.

Redistribution of Pulmonary Blood Flow Impacts Thermodilution-based Extravascular Lung Water Measurements in a Model of Acute Lung Injury

Studies using transthoracic thermodilution have demonstrated increased extravascular lung water (EVLW) measurements attributed to progression of edema and flooding during sepsis and acute lung injury. The authors hypothesized that redistribution of pulmonary blood flow can cause increased apparent EVLW secondary to increased perfusion of thermally silent tissue, not increased lung edema. Anesthetized, mechanically ventilated canines were instrumented with PiCCO (Pulsion Medical, Munich, Germany) catheters and underwent lung injury by repetitive saline lavage. Hemodynamic and respiratory physiologic data were recorded. After stabilized lung injury, endotoxin was administered to inactivate hypoxic pulmonary vasoconstriction. Computed tomographic imaging was performed to quantify in vivo lung volume, total tissue (fluid) and air content, and regional distribution of blood flow. Lavage injury caused an increase in airway pressures and decreased arterial oxygen content with minimal hemodynamic effects. EVLW and shunt fraction increased after injury and then markedly after endotoxin administration. Computed tomographic measurements quantified an endotoxin-induced increase in pulmonary blood flow to poorly aerated regions with no change in total lung tissue volume. The abrupt increase in EVLW and shunt fraction after endotoxin administration is consistent with inactivation of hypoxic pulmonary vasoconstriction and increased perfusion to already flooded lung regions that were previously thermally silent. Computed tomographic studies further demonstrate in vivo alterations in regional blood flow (but not lung water) and account for these alterations in shunt fraction and EVLW.

Influence of Rapid Fluid Loading on Airway Structure and Function in Healthy Humans

BackgroundThe present study examined the influence of rapid intravenous fluid loading (RFL) on airway structure and pulmonary vascular volumes using computed tomography imaging and the subsequent impact on pulmonary function in healthy adults (n = 16). Methods and ResultsTotal lung capacity (ΔTLC = −6%), forced vital capacity (ΔFVC = −14%), and peak expiratory flow (ΔPEF = −19%) decreased, and residual volume (ΔRV = +38%) increased post-RFL (P < .05). Airway luminal cross-sectional area (CSA) decreased at the trachea, and at airway generation 3 (P < .05), wall thickness changed minimally with a tendency for increasing in generation five (P = .13). Baseline pulmonary function was positively associated with airway luminal CSA; however, this relationship deteriorated after RFL. Lung tissue volume and pulmonary vascular volumes increased 28% (P < .001) post-RFL, but did not fully account for the decline in TLC. ConclusionsThese data suggest that RFL results in obstructive/restrictive PF changes that are most likely related to structural changes in smaller airways or changes in extrapulmonary vascular beds.

Noninvasive quantification of heterogeneous lung growth following extensive lung resection by high-resolution computed tomography

To quantify the in vivo magnitude and distribution of regional compensatory lung growth following extensive lung resection, we performed high-resolution computed tomography at 15- and 30-cmH(2)O transpulmonary pressures and measured air and tissue (including microvascular blood) volumes within and among lobes in six adult male foxhounds, before and after balanced 65% lung resection ( approximately 32% removed from each side). Each lobe was identified from lobar fissures. Intralobar gradients in air and tissue volumes were expressed along standardized x,y,z-coordinate axes. Fractional tissue volume (FTV) was calculated as the volume ratio of tissue/(tissue + air). Following resection compared with before, lobar air and tissue volumes increased 1.8- to 3.5-fold, and whole lung air and tissue volumes were 67 and 90% of normal, respectively. Lobar-specific compliance doubled post-resection, and whole lung-specific compliance normalized. These results are consistent with vigorous compensatory growth in all remaining lobes. Compared with pre-resection, post-resection interlobar heterogeneity of FTV, assessed from the coefficient of variation, decreased at submaximal inflation, but was unchanged at maximal inflation. The coefficient of variation of intralobar FTV gradients changed variably due to the patchy development of thickened pleura and alveolar septa, with elevated alveolar septal density and connective tissue content in posterior-caudal and peripheral regions of the remaining lobes; these areas likely experienced disproportional mechanical stress. We conclude that HRCT can noninvasively and quantitatively assess the magnitude and spatial distribution of compensatory lung growth. Following extensive resection, heterogeneous regional mechanical lung strain may exceed the level that could be sustained solely by existing connective tissue elements.

Computed Tomography in Pulmonary Evaluation of Children with Acyanotic Congenital Heart Defect and Pulmonary Hyperflow

Respiratory dysfunction is common in children with acyanotic congenital heart defects (ACHD) with pulmonary hyperflow; however, little is known about the pulmonary structure of those patients. The objective of this study was to quantify the volumes of air and tissue, as well as the distribution of pulmonary aeration in this population. After approval by the Ethics Committee of the institution and signing of an informed consent, seven children with ACHD with pulmonary hyperflow underwent computed tomographies of the chest. All images included the left and right pulmonary contour, and pulmonary volumes and weight were calculated using volumetric data. Paired Student t test was used to compare left and right, and exponential regression was used for correlations. Patients had a mean age of 20 months and weight of 9.9 kg. Total pulmonary volume (TPV) was 66.7 +/- 23.1 mL.kg-1, tissue volume of 33.5 +/- 15.7 mL.kg-1, and air volume of 33.1 +/- 8.3 mL.kg-1. The right lung represented 57.9% of TPV and the left, 42.1% (p < 0.001). The pulmonary volume of air on the right was 60.5% of the total air volume (p < 0.001), and the volume of pulmonary parenchyma normally aerated was significantly lower on the left (27.6 +/- 6.8 vs . 18.1 +/- 8%, p < 0.001). The volume of lung tissue was greater than expected in children with ACHD with pulmonary hyperflow, possibly due to interstitial edema. Pulmonary aeration is reduced in the left lung due to the compression of the lung by the heart.