The Estimation of Lung Mechanics Parameters in the Presence of Pathology: A Theoretical Analysis

Mechanical lung function is frequently assessed in terms of lung resistance (R _L), lung elastance (E _L), and airway resistance (R _aw). These quantities are determined by measuring input impedance at various oscillation frequencies, and allow lung tissue resistance (R _t) to be estimated as the difference between R _L and R _aw. These various parameters change in characteristic ways in the presence of lung pathology. In particular, the ratio R _t/E _L (known as hysteresivity, (η) has been shown both experimentally and in numerical simulations to increase when regional heterogeneities in mechanical function develop throughout the lung. In this study, we performed an analytical investigation of a two-compartment lung model and showed that while heterogeneity always leads to an increase in E _L, η will increase only initially. When heterogeneity becomes extreme, η stops increasing and starts to decrease. However, there are no experimental reports of η decreasing under conditions in which heterogeneity would be expected to exist. We speculate that this is because liquid bridges invariably form across airway lumen that narrow to a certain point, thereby preventing them from achieving arbitrarily small non-zero radii. We also show that recruitment of closed lung units during lung inflation may lead to variables responses in both η and E _L.     

Interleukin-1 receptor antagonist restores homeostatic function and limits multiorgan damage in heatstroke

We measured diffusing capacity (DLCO), alveolar membrane properties (D _m), capillary lung volume (V _c), and alveolar volume (V _A ) in 20 healthy subjects (12 males; age 32.4 ± 13 (SD); BMI 21.7 ± 3; non smokers) at total lung capacity (TLC) and at ∼80, 60, and 40% TLC. In all subjects, D _m increased with lung volume, the increase being significantly greater for higher values of D _m(TLC): the inter-individual differences can be interpreted by a greater number of alveolar units coupled to a lower thickness of the air–blood barrier (thus a higher alveolar surface to thickness ratio S _A/τ). On the average, the volume-dependent increase of D _m from ∼40 to 100% TLC is less than expected based on geometrical increase of S _A /τ. In fact, up to ∼80% TLC, the increase in D _m closely reflects only the increase of S _A, suggesting “unfolding” of the septa with no appreciable decrease in τ. Conversely, above 80% TLC, the decrease in τ due to parenchymal stretching becomes the main factor affecting D _m. In all subjects, V _c decreased with increasing lung volume, in line with an increase in parenchymal stretching; the decrease was significantly larger for higher values of V _c (40% TLC). Possibly reflecting differences in alveolar capillary density. No correlation was found between D _m(TLC) and V _c(40%TLC). The individual specificity in the lung volume dependence of V _c and D _m can be reasonably described by evaluating the V _c/D _m ratio at TLC and at ∼40%TLC.     

Bronchoconstriction during alveolar hypocapnia and systemic hypercapnia in dogs with a cardiopulmonary bypass

The roles of the alveolar and systemic CO₂ on the lung mechanics were investigated in dogs subjected to cardiopulmonary bypass. Low-frequency pulmonary impedance data (Z_L) were collected in open-chest dogs with an alveolar CO₂ level (FA_CO2)$(\text{F}{\text{A}}_{\text{C}{\text{O}}_2})$ of 0.2–7% and during systemic hypercapnia before and after elimination of the vagal tone. Airway resistance (R_aw), inertance (I_aw), parenchymal damping (G) and elastance (H) were estimated from the Z_L. The highest R_aw observed at 0.2% FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$, which decreased markedly up to a FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$ of 2% (212 ± 24%), and remained unchanged under normo- and hypercapnia (FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$ 2–7%). These changes were associated with smaller decreases in I_aw (−16.6 ± 3.7%), mild elevations in G (25.7 ± 4.7%), and no change in H. Significant increases in all mechanical parameters were observed following systemic hypercapnia; atropine counteracted the R_aw rises. We conclude that severe alveolar hypocapnia may contribute to minimization of the ventilation–perfusion mismatch by constricting the airways in poorly perfused lung regions. The constrictor potential of systemic hypercapnia is mediated by vagal reflexes.     

The augmented RIC model of the human respiratory system

This paper describes the augmented RIC model of respiratory impedance and analyzes its parameter values estimated—by a modified Newton method with least squares criterion—from impulse oscillometry data. The data were from asthmatic children, tested pre- and post-bronchodilator, and from healthy adults and a second group of adults with COPD. Our analyses show that the augmented RIC model was 13.7–66.6% more accurate than the extended RIC model at fitting these data, while its parameter estimates were within previously reported ranges, unlike the Mead1969, DuBois and Mead models, which typically yielded compliance estimates exceeding 200 l/kPa. Additionally, the augmented RIC model’s C _p parameter, representing peripheral airway compliance, is a statistically significant discriminator between unconstricted and constricted conditions (with p < 0.001) occurring in asthma and COPD. This corresponds well with current medical understanding, so the augmented RIC model is potentially useful for detection and treatment of airflow obstruction.     

Single-breath diffusing capacities for NO, CO and C18O2 in rabbits

 Nitric oxide (NO) has been introduced recently for studying alveolar-capillary gas transfer. Due to extremely fast reaction kinetics for the association of NO with haemoglobin, pulmonary NO uptake is expected to depend only on diffusion, whereas in the case of carbon monoxide (CO) or oxygen-labelled carbon dioxide (C¹⁸O₂) the alveolar-capillary transfer is, in addition, known to depend on a blood uptake component. To provide further data for NO, CO and C¹⁸O₂, we determined the pulmonary diffusing capacities (D _L) for the indicator gases mentioned, performing single-breath manoeuvres on ten rabbits. The inspired gas mixtures contained 0.05% NO and/or 0.2% CO or 1% C¹⁸O₂ in nitrogen. Applying respiratory mass spectrometry to the expirates we obtained the following mean ± SD values: D _L,NO/D _L,CO = 3.55 ± 0.4, D _L,C18O2/D _L,NO = 6.0 ± 0.6, D _L,C18O2/D _L,CO = 21.4 ± 2.5. Graham’s law predicts D _L ratios of 1.9 for NO/CO, 12 for C¹⁸O₂/NO, and 23 for C¹⁸O₂/CO. Thus we equally underestimated the predicted D _L ratios for C¹⁸O₂/NO and CO/NO by a factor of approximately 0.5. From this, and by excluding significant interactions between the indicator gases and lung tissues, we conclude that the closest approximation of the diffusive component of D _L is indeed obtained by using NO. Received: 13 May 1997 / Received after revision: 13 August 1997 / Accepted: 22 August 1997     

Glycemic control influences lung membrane diffusion and oxygen saturation in exercise-trained subjects with type 1 diabetes: alveolar-capillary membrane conductance in type 1 diabetes

Lung diffusing capacity (DLCO) is influenced by alveolar-capillary membrane conductance (D _M) and pulmonary capillary blood volume (V _C), both of which can be impaired in sedentary type 1 diabetes mellitus (T1DM) subjects due to hyperglycemia. We sought to determine if T1DM, and glycemic control, affected DLNO, DLCO, D _M, V _C and SaO₂ during maximal exercise in aerobically fit T1DM subjects. We recruited 12 T1DM subjects and 18 non-diabetic subjects measuring DLNO, DLCO, D _M, and V _C along with SaO₂ and cardiac output (Q) at peak exercise. The T1DM subjects had significantly lower DLCO/Q and D _M/Q with no difference in Q, DLNO, DLCO, D _M, or V _C (DLCO/Q = 2.1 ± 0.4 vs. 1.7 ± 0.3, D _M/Q = 2.8 ± 0.6 vs. 2.4 ± 0.5, non-diabetic and T1DM, p < 0.05). In addition, when considering all subjects there was a relationship between DLCO/Q and SaO₂ at peak exercise (r = 0.46, p = 0.01). Within the T1DM group, the optimal glycemic control group (HbA1c <7%, n = 6) had higher DLNO, DLCO, and D _M/Q than the poor glycemic control subjects (HbA1c ≥7%, n = 6) at peak exercise (DLCO = 38.3 ± 8.0 vs. 28.5 ± 6.9 ml/min/mmHg, DLNO = 120.3 ± 24.3 vs. 89.1 ± 21.0 ml/min/mmHg, D _M/Q = 3.8 ± 0.8 vs. 2.7 ± 0.2, optimal vs. poor control, p < 0.05). There was a negative correlation between HbA1c with DLCO, D _M and D _M/Q at peak exercise (DLCO: r = −0.70, p = 0.01; D _M: r = −0.70, p = 0.01; D _M/Q: r = −0.68, p = 0.02). These results demonstrate that there is a reduction in lung diffusing capacity in aerobically fit athletes with T1DM at peak exercise, but suggests that maintaining near-normoglycemia potentially averts lung diffusion impairments.     

Respiratory impedance spectral estimation for digitally created random noise

Measurement of respiratory input mechanical impedance (Z_rs) is noninvasive, requires minimal subject cooperation, and contains information related to mechanical lung function. A common approach to measure Z_rs is to apply random noise pressure signals at the airway opening, measure the resulting flow variations, and then estimate Z_rs using Fast-Fourier Transform (FFT) techniques. The goal of this study was to quantify how several signal processing issues affect the quality of a Z_rs spectral estimate when the input pressure sequence is created digitally. Random noise driven pressure and flow time domain data were simulated for three models, which permitted predictions of Z_rs characteristics previously reported from 0–4, 4–32, and 4–200 Hz. Then, the quality of the Z_rs estimate was evaluated as a function of the number of runs ensemble averaged, windowing, flow signal-to-noise ratio (SNR), and pressure spectral magnitude shape |P(jω)|. For a |P(jω)| with uniform power distribution and a SNR<100, the 0–4 Hz and 4–200 Hz Z_rs estimates for 10 runs were poor (minimum coherence γ²<0.75) particularly where Z_rs is high. When the SNR>200 and 10 runs were averaged, the minimum γ² >0.95. However, when |P(jω)| was matched to |Z_rs|, γ² > 0.91 even for 5 runs and a SNR of 20. For data created digitally with equally spaced spectral content, the rectangular window was superior to the Hanning. Finally, coherence alone may not be a reliable measure of Z_rs quality because coherence is only an estimate itself. We conclude that an accurate estimate of Z_rs is best obtained by matching |P(jω)| to |Z_in| (subject and speaker) and using rectangular windowing.     

Effect of the underwater torque on the energy cost,drag and efficiency of front crawl swimming

Underwater torque (T′) is defined as the product of the force with which the swimmer's feet tend to sink times the distance between the feet and the centre of volume of the lungs. It has previously been shown that experimental changes ofT′, obtained by securing around the swimmer's waist a plastic tube filled, on different occasions, with air, water or 2-kg lead, were accompanied by changes in the energy cost of swimming per unit of distance (C_S) at any given speed. The aim of this study was to investigate whether the observed increases of C_S withT′ during front crawl swimming were due to an increase of active body drag (D_b), a decrease of drag efficiency (η_d) or both. The effect of experimental changes ofT′ on C_S, D_b and η_d were therefore studied on a group of eight male elite swimmers at two submaximal speeds (1.00 and 1.23 m · s⁻¹). To compare different subjects and different speeds, the individual data for C_S, D_b,η_d andT′ were normalized dividing them by the corresponding individual averages. These were calculated from all individual data (of C_S, D_b, η_d andT′) obtained from that subject at that speed. It was found that, between the two extremes of this study (tube filled with air and with 2-kg lead),T′ increased by 73% and that C_S, D_b and η_d increased linearly withT′. The increase of C_S between the two extremes was intermediate ( ≈ 20%) between that of D_b (≈ 35%) and of η_d ( ≈ 16%). Thus, the actual strategy implemented by the swimmers to counteractT′, was to tolerate a large increase of D_b. This led also to a substantial (albeit smaller) increase of did, the effect of which was to reduce the increase of C_S that would otherwise have occurred.     

Serial distribution of airway diameters from input impedance and computed tomography

Indirect measures of airway diameter such as respiratory system input impedance (Z _in) have been widely used to infer or quantify bronchoconstriction, or bronchodilation. One such measure,Z _in above 100 Hz has been shown to be primarily influenced by airway geometry and airway walls but not by lung and chest wall tissues. We used a recently developed method based on a complex asymmetrically branched network of tubes with nonrigid walls to analyzeZ _in from 100 to 2,000 Hz in control and bronchoconstricted (histamine injection) dogs. The resulting estimates of airway diameters indicated that peripheral airways were constricted far more (≈30% of their control diameters) than central airways (i.e., 0% in the trachea). Separate measurements of changes in airway diameters were made in an excised dog lung using high resolution computed tomography. The observed changes in airway diameter between lung volumes of total lung capacity (TLC) and functional residual capacity (FRC) were quantitatively consistent with those obtained fromZ _indata in our control dogs atFRC. We conclude that this systems identification method can be used to estimate the distribution of airway diameters fromZ _in. An erratum to this article is available at .     

Energy cost and mechanical efficiency of riding a four-wheeled, human-powered, recumbent vehicle

Oxygen consumption at steady state (V˙O ₂, l · min⁻¹) and mechanical power (W˙, W) were measured in five subjects riding a human-powered vehicle (HPV, the Karbyk, a four-wheeled recumbent cycle) on a flat concrete road at constant sub-maximal speeds. The external mechanical work spent per unit of distance (W, J · m⁻¹), as calculated from the ratio of W˙ to the speed (v, m · s⁻¹), was found to increase with the square of v: W˙=8.12+(0.262 ·v ²) (r=0.986, n=31), where the first term represents the mechanical energy wasted, over a unit of distance, against frictional forces (rolling resistance, R_r), and the second term (k · v ²) is the work performed, per unit distance, to overcome the air drag. The rolling coefficient (C_r, obtained dividing R_r by m · g, where m is the overall mass and g is the acceleration of gravity) amounted to [mean (SD)] 0.0084 (0.0008), that is about 60% higher than that of a racing bicycle. The drag coefficient was calculated from the measured values of k, air density (ρ) and frontal area (A) [C_x=k · (0.5 · A · ρ)⁻¹], and amounted to 1.067 (0.029), that is about 20% higher than that of a racing bicycle. The energy cost of riding the HPV (C_k, J · m⁻¹) was measured from the ratio of metabolic power above rest (net V˙O ₂, expressed in J · s⁻¹) to the speed (v, m · s⁻¹); the value of this parameter increased with the square of v, as described by: C_k=61.45 + (0.675 · v ²) (r=0.711, n=23). The net mechanical efficiency (η) was calculated from the ratio of W to C_k: over the investigated speed range this turned out to be 0.22 (0.021). Best performance times (BPTs) of a “typical”élite athlete riding the Karbyk were calculated over the distances of 1, 5 and 10 km: these were about 8% longer than the BPTs calculated, on the same subjects, when riding a conventional racing bicycle. Accepted: 7 August 2000     

Morphine decreases the voltage sensitivity of slow sodium channels

Cell membrane recordings were made in conditions of voltage clamping with tight attachment of the microelectrode—patch clamping— to study the effects of morphine on tetrodotoxin-resistant (TTX_r) sodium channels in rat spinal ganglion neurons in culture. The effects of a number of biologically active substances which regulate the receptor-mediated actions of morphine were studied. The effects of morphine were found to involve a chain of sequential reactions leading to decreases in the transfer of effective charge (Z_eff) by the activatory gate system of TTX_r sodium channels, depending on the concentration of agonist in the extracellular solution. A value of 8 nM was obtained forK _D , with a Hill coefficient of X=0.5. Non-specific antagonists of opioid receptors blocked the actions of morphine; these included ouabain at a concentration of 100 μM. An inhibitor, and activator, and a blocker of G-proteins had no effect on the effective charge. These data provide evidence that morphine decreases the voltage sensitivity of TTX_r sodium channels. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 2, pp. 225–236, February, 1999.     

Validity of bioelectrical impedance and ultrasonographic methods for estimating the muscle volume of the upper arm

The present study aimed to investigate the validity of bioelectrical impedance and ultrasonographic methods for predicting the muscle volume of the upper arm. Bioelectrical impedance of the right upper arm and the thickness of elbow flexor and extensor muscles were measured from 26 healthy young adult men using a specially designed bioelectrical impedance data acquisition system and brightness-mode ultrasound apparatus, respectively. As reference data, the muscle volume (MV_MRI) of the right upper arm was determined using a magnetic resonance imaging method. The impedance index was calculated as L ²/Z, where L is the upper arm length and Z is the impedance of the shoulder to the elbow. The muscle volume (MV_ULT) was calculated as π·(d/2)²·L, where d is muscle thickness. L ²/Z and MV_ULT were significantly correlated with MV_MRI with correlation coefficients of 0.971 and 0.962, respectively. In these relationships, the standard errors of estimation were 44.2 cm³ (6.3%) for L ²/Z and 50.7 cm³ (7.2%) for MV_ULT. There was no significant difference between the absolute errors of muscle volumes estimated by L ²/Z and MV_ULT: 36.2 (4.8, SEM) cm³ for L ²/Z versus 40.3 (5.8) cm³ for MV_ULT. The present results suggest that both bioelectrical impedance and ultrasonographic methods may be useful for predicting the muscle volume of the upper arm. Accepted: 7 March 2000     

Measurement of Solute Transport in the Endothelial Glycocalyx Using Indicator Dilution Techniques

A new method is presented to quantify changes in permeability of the endothelial glycocalyx to small solutes and fluid flow using techniques of indicator dilution. Following infusion of a bolus of fluorescent solutes (either FITC or FITC conjugated Dextran70) into the rat mesenteric circulation, its transient dispersion through post-capillary venules was recorded and analyzed offline. To represent dispersion of solute as a function of radial position in a microvessel, a virtual transit time (VTT) was calculated from the first moment of fluorescence intensity–time curves. Computer simulations and subsequent in vivo measurements showed that the radial gradient of VTT within the glycocalyx layer (ΔVTT/Δr) may be related to the hydraulic resistance within the layer along the axial direction in a post-capillary venule and the effective diffusion coefficient within the glycocalyx. Modeling the inflammatory process by superfusion of the mesentery with 10⁻⁷ M fMLP, ΔVTT/Δr was found to decrease significantly from 0.23 ± 0.08 SD s/μm to 0.18 ± 0.09 SD s/μm. Computer simulations demonstrated that ΔVTT/Δr is principally determined by three independent variables: glycocalyx thickness (δ), hydraulic resistivity (K _r) and effective diffusion coefficient of the solute (D _eff) within the glycocalyx. Based upon these simulations, the measured 20% decrease in ΔVTT/Δr at the endothelial cell surface corresponds to a 20% increase in D _eff over a broad range in K _r, assuming a constant thickness δ. The absolute magnitude of D _eff required to match ΔVTT/Δr between in vivo measurements and simulations was found to be on the order of 2.5 × 10⁻³ × D _free, where D _free is the diffusion coefficient of FITC in aqueous media. Thus the present method may provide a useful tool for elucidating structural and molecular alterations in the glycocalyx as occur with ischemia, metabolic and inflammatory events.     

Energy cost and efficiency of Venetian rowing on a traditional,flat hull boat (<Emphasis Type="Italic">Bissa</Emphasis>)

The total net metabolic power output (, kW) required to scull a traditional, flat hull boat—the “Bissa”, 9.02 m long and weighting about 500 kg including the crew—was assessed at different constant speeds (ν) ranging from 2.44 to 3.75 m s⁻¹. increased with the speed:  = 0.417 × e ^0.664v ; r ² = 0.931. The amount of metabolic energy spent per unit distance (C, J m⁻¹) to move the “Bissa”, calculated by dividing by the corresponding ν, was a linear function of ν: C = 0.369 ν –0.063; r ² = 0.821. The hydrodynamic resistance met by the boat in the water—drag (D, N)—was estimated by analysing the decay of the reciprocal of ν as a function of time measured during several spontaneous deceleration tests carried out in still water and by knowing the total mass of the watercraft plus crew. D increased as a square function of speed: D = 12.76 v ². This allowed us to calculate the drag efficiency (η_d), as the ratio of D to C: η_d increased from 8.9 to 13.7% in the range of the speeds tested. The “Bissa” turned out to be as economical as other flat hull, traditional watercrafts, such as the bigger Venetian gondola, and her η_d was similar to that of other modern and traditional watercrafts.     

Spatial Distribution of Human Respiratory System Transfer Impedance

Transfer impedance (Z _tr) of the respiratory system provides specific information on airways and tissues, but little is known about its spatial distribution in the different thoracoabdominal regions. To study Z _tr distribution on the chest wall surface we analyzed five healthy subjects in the supine position by applying a sinusoidal forcing pressure (4, 8, and 12 Hz) at the mouth and measuring airway opening pressure and flow. Three-dimensional positions of 68 reflective markers placed on the chest wall over selected reference points were simultaneously measured by an optoelectronic motion analyzer. A subset of ten points placed on the midline were used to measure chest wall movements in the craniocaudal direction. While the motion of rib cage markers was synchronous, the abdominal markers demonstrated surface waves propagating caudally. The amplitude and phase of these waves were strongly dependent on position and frequency. We used a new method to measure total and local chest wall volume variations to compute the distribution of Z _tr over the chest wall. Above 4 Hz we found that Z _tr was inhomogeneously distributed and strongly dependent on position and frequency, mainly in the abdomen where the phase was often 180° with high values of modulus. For this reason, we conclude that above 8 Hz Z _tr represents rib cage mechanics almost exclusively. © 2003 Biomedical Engineering Society. PAC2003: 8719Uv, 8780-y     

Bopindolol, pindolol, and atenolol in patients with chronic obstructive lung disease

Summary Twelve subjects with chronic obstructive lung disease and a partially reversible obstruction received increasing single doses of bopindolol (1, 2, 4, and 8 mg), pindolol (7.5, 15, and 30 mg), and atenolol (50 and 100 mg). Resting heart rate and blood pressure were reduced in a dose-dependent fashion. The actions of the drugs on lung function were assessed by whole body plethysmography. Pindolol did not influence mean airway resistance (R _aw). Bopindolol (1, 2 and 4 mg) and atenolol (50 mg) exhibited a neutral effect on meanR _aw. Atenolol (100 mg) and to a lesser extent bopindolol (8 mg) induced a long-lasting increase in mean R_aw.Abbreviations R_aw airway resistance - HR heart rate     

Energy cost and efficiency of sculling a Venetian gondola

Summary Oxygen uptake was measured on four male subjects during sculling gondolas at constant speeds from 1 to 3 m · s^–1. The number of scullers on board in the different trials was one, two or four. Tractional water resistance (drag,D, N) was also measured in the same range of speeds. Energy cost of locomotion per unit of distance (C, J·m^–1), as calculated from the ratio of O₂ uptake above resting to, increased with v according to a power function (C=155.2· ^1.67;r=0.88). AlsoD could be described as a power function of the speed:D=12.3· ^2.21;r= 0.94). The overall efficiency of motion, as obtained from the ratio ofD toC increased with speed from 9.2% at 1.41 m· s^–1 to 14.5% at 3.08 m·s^–1. It is concluded that, in spite of this relatively low efficiency of motion, the gondola is a very economic means. Indeed, at low speeds ( 1 m·s^–1), the absolute amount of energy for propelling a gondola is the same as that for waking on the level at the same speed for a subject of 70 kg body mass.     

Dose-guided radiotherapy for lung tumors

The transit in vivo dosimetry performed by an electronic portal imaging device (EPID) is a very practical method to check error sources in radiotherapy. Recently, the present authors have developed an in vivo dosimetry method based on correlation functions, F (w, L), defined as the ratio between the transit signal, S _t (w, L), by the EPID and the mid-plane dose, D _m (w, L), in a solid water phantom as a function of the phantom thickness, w, and of the field dimensions, L. In particular, generalized correlation functions F (w, L) for 6, 10 and 15 MV X-ray beams supplied by a pilot Varian linac, are here used by other three linacs operating in two centers. This way the workload, due to measurements in solid water phantom, needed to implement the in vivo dosimetry method was avoided. This article reports a feasibility study on the potentiality of this procedure for the adaptive radiotherapy of lung tumors treated by 3D conformal radiotherapy techniques. In particular, the dose reconstruction at the isocenter point D _iso in the lung tumor has been used as dose-guided radiotherapy (DGRT), to detect the inter-fraction tumor anatomy variations that can require new CT scans and an adaptive plan. When a difference greater than 6% between the predicted dose by the treatment planning system (TPS), D _iso,TPS and the D _iso was observed, the clinical action started to detect possible anatomical lung tumor changes. Twelve over twenty patients examined presented in vivo dose discrepancies due to the tumor morphological changes during treatments, and these results were successively confirmed by new CT scans. In this work, for a patient that showed for all beams, D _iso values over the tolerance level, the new CT scan was used for an adaptive plan. The lung dose volume histogram for D _iso,TPS = 2 Gy per fraction suggested the adaptive plan. In particular, the lung volume included in 2 Gy increased from 350 cm³ of the original plan to 550 cm³ of the hybrid plan, while for the adaptive plan the lung volume included in 2 Gy decreased to 15 cm³. Moreover, the mean doses to the organs at risk were reduced to 70%. The results of this research show that the DGRT procedure by the D _iso reconstruction, integrated with radiological imaging, was feasible for periodic investigation on morphological lung tumor changes. This feasibility study takes into account the accuracy of two algorithms based on the pencil beam and collapsed cone convolution models for dose calculations where large density inhomogeneities are present.     

Biased cell migration of fibroblasts exhibiting contact guidance in oriented collagen gels

We present here the first quantitative correlation for cell contact guidance in an oriented fibrillar network in terms of biased cell migration. The correlation is between the anisotropic cell diffusion parameter,D _A=D_x/D_y, and the collagen gel birefringence, Δn, a measure of axially biased collagen fibril orientation in thex-direction. The cell diffusion coefficients,D _x andD _y, measure the dispersal of cells in the directions coincident with and normal to the axis of fibril orientation, respectively. Three essential methodological components are involved: (i) exploiting the orienting effect of a magnetic field on collagen fibrils during fibrillogenesis to systematically prepare uniform axially oriented collagen gels; (ii) using a microscope/image analysis workstation with precise, computer-controlled rotating and translating stages to automate birefringence measurement and, along with rapid “coarse optical sectioning” via digital image processing, to enable 3-D cell tracking of many cells in multiple samples simultaneously; and (iii) employing a rigorous statistical analysis of the cell tracks to estimate the magnitude and precision of the direction-dependent cell diffusion coefficients,D _x andD _y, that defineD _A. We find that this measure of biased migration in contact guidance (D _A) increases with increasing collagen fibril orientation (Δn) due mainly to a rapid enhancement of migration along the axis of fibril orientation at low levels of fibril orientation, and to a continued suppression of migration normal to the axis of fibril orientation at high levels of fibril orientation.