The core apoptotic executioner proteins CED-3 and CED-4 promote initiation of neuronal regeneration in Caenorhabditis elegans.

A critical accomplishment in the rapidly developing field of regenerative medicine will be the ability to foster repair of neurons severed by injury, disease, or microsurgery. In C. elegans, individual visualized axons can be laser-cut in vivo and neuronal responses to damage can be monitored to decipher genetic requirements for regeneration. With an initial interest in how local environments manage cellular debris, we performed femtosecond laser axotomies in genetic backgrounds lacking cell death gene activities. Unexpectedly, we found that the CED-3 caspase, well known as the core apoptotic cell death executioner, acts in early responses to neuronal injury to promote rapid regeneration of dissociated axons. In ced-3 mutants, initial regenerative outgrowth dynamics are impaired and axon repair through reconnection of the two dissociated ends is delayed. The CED-3 activator, CED-4/Apaf-1, similarly promotes regeneration, but the upstream regulators of apoptosis CED-9/Bcl2 and BH3-domain proteins EGL-1 and CED-13 are not essential. Thus, a novel regulatory mechanism must be utilized to activate core apoptotic proteins for neuronal repair. Since calcium plays a conserved modulatory role in regeneration, we hypothesized calcium might play a critical regulatory role in the CED-3/CED-4 repair pathway. We used the calcium reporter cameleon to track in vivo calcium fluxes in the axotomized neuron. We show that when the endoplasmic reticulum calcium-storing chaperone calreticulin, CRT-1, is deleted, both calcium dynamics and initial regenerative outgrowth are impaired. Genetic data suggest that CED-3, CED-4, and CRT-1 act in the same pathway to promote early events in regeneration and that CED-3 might act downstream of CRT-1, but upstream of the conserved DLK-1 kinase implicated in regeneration across species. This study documents reconstructive roles for proteins known to orchestrate apoptotic death and links previously unconnected observations in the vertebrate literature to suggest a similar pathway may be conserved in higher organisms.

Ivermectin and milbemycin oxime in experimental adult heartworm (Dirofilaria immitis) infection of dogs.

BACKGROUND: The US Food and Drug Administration reports an increase in the frequency of reports of lack of effectiveness claims for heartworm (HW) prevention products. HYPOTHESIS: At their labeled doses, single doses of commercially available HW prevention products are not completely effective against all field isolates of HW. ANIMALS: Forty-two HW-free dogs experimentally inoculated with a recent HW field isolate. METHODS: Placebo-controlled, blinded laboratory clinical trial. Dogs randomly allocated to 1 of 3 treatment groups with 14 dogs per group. Groups were untreated control or p.o. dosed with milbemycin oxime (MBO) or ivermectin (IVM). Dogs were inoculated with 50 HW third stage larvae 30 days before dosing and necropsy was performed on Day 123 after treatment to enumerate adult HW. RESULTS: Thirteen of 14 control dogs had adult HW detected at necropsy with a geometric mean worm count of 22.3. One HW was found in 1 dog in each of the MBO and IVM treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Two currently approved macrocyclic lactone HW preventives used at their labeled dose rates were <100% effective against a recent HW field isolate, supporting the hypothesis that the effectiveness of a single dose of these preventives can vary. This is important in guiding clients on expectations of product effectiveness.

Fibronectin expression modulates mammary epithelial cell proliferation during acinar differentiation.

The mammary gland consists of a polarized epithelium surrounded by a basement membrane matrix that forms a series of branching ducts ending in hollow, sphere-like acini. Essential roles for the epithelial basement membrane during acinar differentiation, in particular laminin and its integrin receptors, have been identified using mammary epithelial cells cultured on a reconstituted basement membrane. Contributions from fibronectin, which is abundant in the mammary gland during development and tumorigenesis, have not been fully examined. Here, we show that fibronectin expression by mammary epithelial cells is dynamically regulated during the morphogenic process. Experiments with synthetic polyacrylamide gel substrates implicate both specific extracellular matrix components, including fibronectin itself, and matrix rigidity in this regulation. Alterations in fibronectin levels perturbed acinar organization. During acinar development, increased fibronectin levels resulted in overproliferation of mammary epithelial cells and increased acinar size. Addition of fibronectin to differentiated acini stimulated proliferation and reversed growth arrest of mammary epithelial cells negatively affecting maintenance of proper acinar morphology. These results show that expression of fibronectin creates a permissive environment for cell growth that antagonizes the differentiation signals from the basement membrane. These effects suggest a link between fibronectin expression and epithelial cell growth during development and oncogenesis in the mammary gland.

Imidacloprid plus moxidectin topical solution for the prevention of heartworm disease (Dirofiloria immitis) in dogs.

A topically applied formulation containing 10% imidacloprid+2.5% moxidectin (Advocate/Advantage multi) has been developed for monthly application to dogs for the prevention of canine heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, mite infestations, and intestinal nematode infections. The efficacy of this formulation to prevent canine HW disease was confirmed at three study locations which included the use of 88 purpose-bred beagles 6-8 months of age. Two of these studies also evaluated the effects of post-treatment water exposure or shampooing on product performance. Each dog was infected with 50 third-stage D. immitis larvae on test days -30 to -45. Dogs were blocked according to gender and body weight on test day -1. Topically applied test articles were administered once on test day 0 as follows: 10% imidacloprid+2.5% moxidectin (52 dogs); 2.5% moxidectin mono solution (eight dogs); 10% imidacloprid mono solution (16 dogs); and placebo solution (12 dogs). Treatment dosages were applied to provide a minimum of 10 mg/kg imidacloprid and/or 2.5 mg/kg moxidectin. Subgroups of dogs were exposed to water to simulate swimming/rain exposure at designated post-treatment intervals. Additional dogs were shampooed at 90 min, 4 h, or 24 h post-treatment. All dogs were necropsied 110-119 days post-treatment for recovery of adult D. immitis. No adult D. immitis were recovered at necropsy from any of the dogs receiving 10% imidacloprid+2.5% moxidectin or 2.5% moxidectin mono solution, demonstrating 100% efficacy for prevention of D. immitis infection. A total of 701 adult D. immitis were recovered at necropsy from dogs receiving 10% imidacloprid mono solution or placebo (range of 11-40 D. immitis/dog). The efficacy of 10% imidacloprid+2.5% moxidectin treatment for the prevention of HW disease was not decreased when dogs were shampooed as early as 90 min post-treatment, or when dogs immersed in water 5 times post-treatment at weekly intervals.

Repeatability of quantitative CT indexes of emphysema in patients evaluated for lung volume reduction surgery.

PURPOSE: To evaluate the repeatability of quantitative computed tomographic (CT) indexes of emphysema and the effect of spirometric gating of lung volume during CT in candidates for lung volume reduction surgery (LVRS). MATERIALS AND METHODS: Initial and same-day repeat routine inspiratory spiral chest CT studies were performed in 29 LVRS candidates (group 1, routine study vs repeat study). In a separate cohort of 29 LVRS candidates, spiral chest CT studies were performed both without and with spirometric gating by using a spirometer to trigger scanning at 90% of vital capacity (group 2, spirometric gating study). In each study, Pearson and intraclass correlation coefficients were calculated to determine the agreement between multiple pairs of whole-lung quantitative CT indexes of emphysema, and mean values were compared with two-tailed paired t tests. RESULTS: Pearson and intraclass correlation coefficients were high for all quantitative CT indexes (all > or = 0.92). No significant differences were found between mean values of quantitative CT indexes in group 1. Variation in quantitative CT results was small but more prominent in group 2 than in group 1. The variation in quantitative CT results was primarily related to differences in lung volume (r(2) as great as 0.83). CONCLUSION: Repeatability of quantitative CT test results in LVRS candidates is high and unlikely to improve by using spirometric gating.

Frequency and CT findings of recurrent disease after lung transplantation.

PURPOSE: To determine the frequency and computed tomographic (CT) findings of recurrence of the primary disease after lung transplantation at six North American lung transplantation centers. MATERIALS AND METHODS: Medical records of 1,394 lung transplant recipients were reviewed to identify patients with recurrent primary disease. Their CT scans and pathologic specimens were reviewed. RESULTS: The frequency of disease recurrence in the six transplantation centers was 1% (15 of 1,394 patients), including six previously reported cases. Sarcoidosis recurred in nine (35%) of 26 transplants and was the most common disease to recur. Three (33%) of nine patients with recurrent sarcoidosis had correlative findings at CT. When present, CT findings were usually different at recurrence compared with pretransplantation CT findings. CONCLUSION: A relatively small percentage of patients are at risk for recurrence of primary disease following lung transplantation. Sarcoidosis is the most common disease to recur.

Evaluation of the speed of kill of fleas and ticks with Frontline Top Spot in dogs.

The speed of kill of a spot-on formulation of fipronil (Frontline Top Spot, Merial Limited, Duluth, GA) against adult cat fleas (Ctenocephalides felis) and brown dog ticks (Rhipicephalus sanguineus) was evaluated in dogs in a commercial laboratory setting. Forty dogs were allocated to 20 replicates of two based on sex and pretreatment flea counts. Within each replicate, dogs were randomly allocated to an untreated control group or to treatment with fipronil, administered topically as a spot-on per label instructions. The technical staff performing the flea and tick counts were unaware of treatment group assignments. Each dog was infested with approximately 100 unfed adult fleas on Day -8 or -6 and on Day -1. Each dog also was infested with approximately 50 unfed adult ticks on Day -1. Treatments were administered on Day 0 according to body weight. Flea and tick counts were performed on four randomly selected dogs from each treatment group at approximately 6, 12, 18, 24, and 48 hours after treatment. Flea and tick count reductions for dogs treated with fipronil were significant (P < .05), as compared with untreated controls, at 18, 24, and 48 hours after treatment. Controlled efficacy of fipronil against C. felis and R. sanguineus ranged from 94% to 100% at these evaluation times. This study demonstrated that the speed of kill of fipronil, applied topically as a spot-on, was 100% against C. felis fleas on dogs within 12 to 18 hours after treatment and 100% against R. sanguineus ticks between 24 and 48 hours after treatment.

Assessment of visually lossless irreversible image compression: comparison of three methods by using an image-comparison workstation.

PURPOSE: To determine the degree of irreversible image compression detectable in conservative viewing conditions. MATERIALS AND METHODS: An image-comparison workstation, which alternately displayed two registered and magnified versions of an image, was used to study observer detection of image degradation introduced by irreversible compression. Five observers evaluated 20 16-bit posteroanterior digital chest radiographs compressed with Joint Photographic Experts Group (JPEG) or wavelet-based trellis-coded quantization (WTCQ) algorithms at compression ratios of 8:1-128:1 and x2 magnification by using (a) traditional two-alternative forced choice; (b) original-revealed two-alternative forced choice, in which the noncompressed image is identified to the observer; and (c) a resolution-metric method of matching test images to degraded reference images. RESULTS: The visually lossless threshold was between 8:1 and 16:1 for four observers. JPEG compression resulted in performance as good as that with WTCQ compression at these ratios. The original-revealed forced-choice method was faster and as sensitive as the two-alternative forced-choice method. The resolution-metric results were robust and provided information on performance above visually lossless levels. CONCLUSION: The image-comparison workstation is a versatile tool for comparative assessment of image quality. At x2 magnification, images compressed with either JPEG or WTCQ algorithms were indistinguishable from unaltered original images for most observers at compression ratios between 8:1 and 16:1, indicating that 10:1 compression is acceptable for primary image interpretation.

Patient selection for lung volume reduction surgery: An objective model based on prior clinical decisions and quantitative CT analysis.

OBJECTIVES: We used whole-lung quantitative CT analysis (QCT)-an objective method of evaluating emphysema severity and distribution based on measurement of lung density-to determine whether subjective selection criteria for lung volume reduction surgery are applied consistently and to model the patient selection process, and assessed the relationship of the model to postoperative outcome. DESIGN: Logistic regression analysis using QCT indexes of emphysema and preoperative physiologic test results as the independent variables, and the decision to operate as the dependent variable. SETTING: University hospital. PATIENTS: Seventy patients selected for bilateral lung volume reduction surgery and 32 otherwise operable patients excluded from surgery based on subjective assessment of emphysema morphology on chest radiography, CT, and perfusion scintigraphy. INTERVENTION: Bilateral lung volume reduction surgery in the selected group. MEASUREMENTS AND RESULTS: Emphysema in patients selected for surgery was more severe overall and in the upper lungs by multiple QCT indexes (p < 0.01, unpaired two-tailed t test). Physiologic abnormalities were slightly more severe in selected patients (p < 0.05, unpaired two-tailed t test). The range of many QCT and physiologic values overlapped considerably between the selected and excluded groups. The percent severe emphysema (<- 960 Hounsfield units [HU]), upper/lower lung emphysema ratio (- 900 HU threshold), and residual volume were the key variables in the model predicting selection decisions (model r(2) = 0.48; p < 0.0001). The model correctly predicted selection decisions in 87% of all cases, 91% of the selected group, and 78% of the excluded group. Surgical patients with a higher model-derived probability of selection had greater postoperative improvement in FEV(1) and 6-min walk distance. CONCLUSIONS: Radiologic selection criteria are applied consistently to the majority of patients. QCT features are strongly associated with selection decisions, are related to outcome, and may help improve consistency and confidence in patient selection.

Detection of CT-proved pulmonary nodules: comparison of selenium-based digital and conventional screen-film chest radiographs.

PURPOSE: To compare hard-copy digital chest radiographs obtained with a selenium-based system with wide-latitude asymmetric screen-film radiographs for detection of pulmonary nodules. MATERIALS AND METHODS: Fifty patients undergoing thoracic computed tomography (CT) for suspected pulmonary nodules were recruited to undergo both digital and screen-film posteroanterior (PA) and lateral chest radiography. Three chest radiologists blinded to the CT results independently reviewed each digital and screen-film radiograph, identified each nodule, and graded their confidence for its presence. RESULTS: Seventy-eight pulmonary nodules (mean diameter, 1.5 cm; range, 0.5-3.5 cm; 62 soft tissue, 16 calcified) were identified with CT in 34 patients, while 16 patients had clear lungs. The mean sensitivity for the detection of all nodules by all readers (PA and lateral) was 66% (95% Cl, 54%, 76%) for digital radiographs and 64% (95% Cl, 52%, 74%) for screen-film radiographs. Differences between the two techniques were not statistically significant (P > .05, Student t test). There was no difference in mean false-positive-true-positive ratios (PA, 0.35; lateral, 0.53) or positive predictive values (PA, 74%; lateral, 65%), and no significant difference (P > .05) was seen in mean reader confidence rating. CONCLUSION: In detecting pulmonary nodules, radiologists perform comparably with selenium-based digital and wide-latitude asymmetric screen-film radiographs.

Perceived fidelity of compressed and reconstructed radiological images: a preliminary exploration of compression, luminance, and viewing distance.

The authors' goal was to explore the impact of image compression algorithm and ratio, image luminance, and viewing distance on radiologists' perception of reconstructed image fidelity. Five radiologists viewed 16 sets of four hard-copy chest radiographs prepared for secondary interpretation. Each set included one uncompressed, and three compressed and reconstructed images prepared using three different algorithms but the same compression ratio. The sets were prepared using two subjects, four compression ratios (10:1, 20:1, 30:1, 40:1), and two luminance levels (2,400 cd/m2, standard lightbox illumination, and 200 cd/m2, simulating a typical CRT display). Readers ranked image quality and evaluated obviousness and clinical importance of differences. Viewing distances for image screening, inspection, and comparison were recorded. At 10:1 compression, the compressed and uncompressed images were nearly indistinguishable; the three algorithms were very similar, and differences were rated "not obvious" and "not important." At higher compression, readers consistently preferred uncompressed images, with notable differences between algorithms. The obviousness and clinical importance of differences were rated higher at lightbox luminance. Viewing distances appeared to be idiosyncratic.

Imaging evaluation of the diaphragm.

The diaphragm performs most of the physiologic work of inspiration, and forms an anatomic barrier between the thoracic and abdominal cavities. Disorders of the diaphragm can be related to impairment of either of these functions, and most have radiologic manifestations. Both intrathoracic and intra-abdominal disease processes can alter the normal radiologic appearance of the diaphragm. Abnormalities are usually first detected on chest radiographs, often incidentally in asymptomatic patients, and many require further characterization by other imaging studies for definitive diagnosis. Fluoroscopy, CT, and MR imaging are frequently the most useful additional studies, whereas ultrasonography, barium contrast studies, and liver-spleen scintigraphy are occasionally helpful. Selection of the most appropriate radiologic technique in a given clinical situation can greatly facilitate the diagnosis of diaphragm abnormalities.

MR analysis of lung volume and thoracic dimensions in patients with emphysema before and after lung volume reduction surgery.

OBJECTIVE: This study was performed to assess the accuracy of determining lung volume in patients with emphysema using MR imaging and then to investigate changes in thoracic dimensions after lung volume reduction surgery. SUBJECTS AND METHODS: Fast gradient-echo breath-hold MR imaging through the entire thorax at full inspiration and expiration was performed in 21 patients with severe emphysema and was performed again in nine of the patients who underwent surgery. Lung volumes were determined using a semiautomated computerized method of delineating the lungs and summing cross-sectional areas. These summed areas were compared with volumes measured on plethysmography and CT. Postoperative changes in thoracic structure were determined by measuring anteroposterior and transverse lung dimensions and lung height before and after surgery. RESULTS: The correlation coefficients and SEM for determining inspiratory lung volume were MR imaging versus plethysmography, r = .77, SEM = -12% (volume measured as less on MR imaging); CT versus plethysmography, r = .86, SEM = -13% (volume measured as less on CT); and MR imaging versus CT, r = .87, SEM = 4% (volume measured as greater on MR imaging). The correlation coefficients and SEM for determining expiratory volume on MR imaging versus plethysmography were r = .77, SEM = 6% (volume measured as greater on MR imaging). After surgery, decreases were found in all thoracic dimensions, and such decreases were greatest at expiration. CONCLUSION: MR measurements of lung volume are comparable with those of CT and differ from those of plethysmography. Changes in thoracic dimensions after lung volume reduction surgery are consistent with improved respiratory mechanics.

Preoperative and postoperative imaging in the surgical management of pulmonary emphysema.

For patients with emphysema, imaging studies have been useful for diagnostic purposes and for preoperative patient selection for surgical intervention, such as bullectomy, lung transplantation, and LVRS. Chest radiography is useful in evaluating hyperinflation. Inspiratory and expiratory films are used to estimate diaphragmatic excursion and air-trapping. CT scan is used to evaluate the anatomy and distribution of emphysema throughout the lungs, providing information clinically unobtainable by other means. Both imaging techniques are useful for detecting other disease processes. Radionuclide lung scanning also provides an estimate of target areas, volume occupying but nonfunctioning lung. Cohort studies utilizing these imaging techniques have demonstrated associations between preoperative characteristics and postoperative outcome. The imaging studies, especially the chest radiograph, have also played an important role in postoperative management. Many other imaging options are available, such as HRCT scan, quantitative CT scan, and single photon emission CT scan. Other techniques, such as MR imaging, may play a future role as well.

Persistent efficacy of doramectin against experimental challenge with Ostertagia ostertagi in cattle.

Two studies were conducted in North America to evaluate the persistent efficacy of doramectin injectable solution against experimental challenge with infective larvae of Ostertagia ostertagi. In both studies, four groups of 10 randomly-assigned calves, negative for trichostrongyle-type eggs on fecal examination, were treated subcutaneously in the midline of the neck with saline (1 ml 50 kg-1) on Day 0 or doramectin (200 micrograms kg-1 = 1 ml 50 kg-1) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. Beginning on Day 14 and continuing through Day 28, the 40 treated calves each were given approximately 1000 infective larvae of O. ostertagi by gavage daily; the two larval-viability monitors were inoculated in a similar manner with approximately 30,000 larvae as a single dose on Day 28. Animals were slaughtered on Day 42 in one study and on Days 42, 43, or 46 in the second. The abomasum from each calf was harvested and processed for worm recovery. A 2% aliquot of abomasal contents plus wash was examined for worm quantification and identification. Geometric mean O. ostertagi burdens were calculated from the log (O. ostertagi count + 1) and were used to estimate percentage reduction. In both studies, doramectin injectable solution was > or = 99.6% efficacious in reducing infection resulting from challenge with infective larvae of O. ostertagi for at least 21 days posttreatment; by 28 days posttreatment, efficacy was 87.3% in one study and 99.7% in the other.

Pulmonary emphysema: comparison of preoperative quantitative CT and physiologic index values with clinical outcome after lung-volume reduction surgery.

PURPOSE: To compare quantitative computed tomographic (CT) and preoperative physiologic values in emphysema with outcome after lung-volume reduction surgery. MATERIALS AND METHODS: In 46 patients, emphysema was quantified by measuring lung attenuation on preoperative CT scans. Quantitative CT and preoperative physiologic values and postoperative outcomes (1-second forced expiratory volume, PaO2, and 6-minute walk distance) were compared. RESULTS: Moderately strong correlations were found between several quantitative CT and preoperative physiologic values (magnitude of r = .29-.58, P < .05) and several quantitative CT and outcome measures (magnitude of r = .31-.47, P < .05). With stratification, postoperative outcome was better with mean lung attenuation greater than -900 HU; 75% or greater of upper lung below -900 HU (emphysema index); greater than 25% of lung below -960 HU (severe emphysema index); ratio of upper- and lower-lung emphysema indexes 1.5 or greater; volume of normally attenuated lung (-850 to -701 HU) greater than 1 L; and full width at half maximum of attenuation-frequency distribution 80 HU or less. Differences in outcome measures between groups stratified with quantitative CT values were often two- to threefold; patients with greater numbers of favorable quantitative CT values had better outcome. Correlations between preoperative physiologic measures and outcome were few. CONCLUSION: In emphysema, quantitative CT values correlate with outcome. Quantitative assessment of emphysema in candidates for lung-volume reduction surgery is potentially useful.

Perfusion scintigraphy in the evaluation for lung volume reduction surgery: correlation with clinical outcome.

PURPOSE: To identify preoperative pulmonary perfusion scintigraphic findings that might be associated with clinical outcomes after lung volume reduction surgery. MATERIALS AND METHODS: Preoperative perfusion scintigrams in 103 patients (56 men, 47 women; age range, 41-76 years; mean age, 61 years +/- 9) were reviewed and graded for emphysematous heterogeneity (from isolated areas to diffuse distribution), extent of maximally perfused lung, and lobar predominance (upper-lobe vs lower-lobe asymmetry). These findings were correlated with clinical outcome on the basis of pulmonary function, arterial blood gas levels, and exercise test results before and 6 months after surgery. RESULTS: Among the 96 patients who survived surgery, there was an average improvement of 47% in the forced expiratory volume in 1 second (FEV1), of 20% in arterial oxygen tension, and of 20% in the 6-minute walking distance. Scintigraphic markers correlated best with FEV1 improvement. The strongest scintigraphic predictor of increase in FEV1 was upper-lobe predominance (r = .38, P < .001), which was followed by heterogeneity (r = .31, P = .002). The seven patients who died had a significantly lower percentage of maximally perfused lung than the survivors (25% vs 34%, P = .004). CONCLUSION: Perfusion scintigraphy can provide modest prognostic information in patients who undergo evaluation for lung volume reduction surgery.

Lung volume reduction surgery: comparison of preoperative radiologic features and clinical outcome.

PURPOSE: To examine the relationship between preoperative radiologic findings and clinical outcome after lung volume reduction surgery. MATERIALS AND METHODS: In 50 consecutive patients, preoperative chest radiographs and computed tomographic (CT) scans were scored by four radiologists for features related to the severity and distribution of emphysema and compared with clinical improvement in forced expiratory volume in 1 second (FEV1), arterial partial pressure of oxygen, and exercise tolerance 6 months after surgery. RESULTS: In the 47 surviving patients, follow-up data showed greater postoperative improvement in function in patients with a global pattern of predominantly upper-lobe emphysema (P < .05) and in patients with a more heterogeneous distribution of emphysema, compressed lung, and a larger percentage of normal and mildly emphysematous lung (P < .05 for improvement in FEV1). Radiographic scores for individual features were more strongly correlated with outcome than CT scores. The combination of upper-lobe severity and percentage of normal and mildly emphysematous lung at CT were the strongest predictors of improvement in FEV1 (r2 = .49). The three patients who died were older (P = .05) and had more severe, diffuse emphysema compared with other patients. CONCLUSION: Imaging studies may help predict the degree of improvement and therefore should be considered an integral part of an objective patient selection process. Radiography alone may be adequate for initial screening.

Patients with emphysema: quantitative CT analysis before and after lung volume reduction surgery. Work in progress.

PURPOSE: To quantitatively assess the morphologic changes in the lungs after lung volume reduction surgery and determine whether changes at quantitative computed tomography (CT) reflect changes in lung function. MATERIALS AND METHODS: In 10 patients, chest CT images were obtained at full inspiration and expiration before and after surgery. A semiautomated segmentation method was developed to isolate the lung regions and calculate the lung volumes and frequency distribution of attenuation values. The changes in lung volume and attenuation after surgery were compared with clinical findings, and an exploratory evaluation of outcome predictors was conducted. RESULTS: Semiautomated segmentation and quantitative analysis compared favorably with manual techniques, and there was good correlation between the emphysema indexes and percentage predicted forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity, and diffusing capacity. The emphysema index decreased from 60% to 38% at inspiration and from 60% to 27% at expiration after surgery. The average CT lung volume decreased from 7.5 to 5.6 L at inspiration (25%) and from 6.4 to 3.8 L (41%) at expiration after surgery and correlated well with measurements at plethysmography. CONCLUSION: Substantial decreases in the lung volumes and emphysema index, increased airflow, possible reexpansion of some remaining lung, and the relation between preoperative quantitative CT indexes and clinical outcome suggest a multifactorial mechanism for improvement seen after surgery.