Publications by authors named "Francesca Pennati"

23 Publications

  • Page 1 of 1

Effects of diaphragmatic control on multiparametric analysis of the sniff nasal inspiratory pressure test and inspiratory muscle activity in healthy subjects.

PLoS One 2021 22;16(7):e0253132. Epub 2021 Jul 22.

PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Empresa Brasileira de Serviços Hospitalares and Departamento de Fisioterapia Universidade Federal do Rio Grande do Norte, Natal, Brazil.

Background: We investigated the influence of diaphragmatic activation control (diaphC) on the relaxation rate, contractile properties and electrical activity of the inspiratory muscles of healthy subjects. Assessments were performed non-invasively using the sniff inspiratory pressure test (SNIP) and surface electromyography, respectively.

Methods: Twenty-two subjects (10 men and 12 women) performed 10 sniff maneuvers in two different days: with and without diaphC instructions. For the SNIP test with diaphC, the subjects were instructed to perform intense activation of the diaphragm. The tests with the best SNIP values were used for analysis.

Results: The maneuver with diaphC when compared to the maneuver without diaphC exhibited significant lower values for: SNIP (p <0.01), maximum relaxation rate (MRR) (p <0.01), maximum rate of pressure development (MRPD) (p <0.01), contraction times (CT) (p = 0.02) and electrical activity of the sternocleidomastoid (SCM) (p <0.01), scalene (SCL) (p = 0.01) and intercostal (CI) (p = 0.03) muscles. In addition, the decay constant (tau, τ) and relaxation time (½ RT) did not present any changes.

Conclusion: The diaphragmatic control performed during the SNIP test influences the inspiratory pressure and the contractile properties of inspiratory muscles. This occurs due to changes in the pattern of muscle recruitment, which change force velocity characteristics of the test. Thus, instruction on diaphC should be encouraged for better performance of the SNIP test and for evaluation targeting the diaphragm muscle activity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253132PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297810PMC
July 2021

Changes in electromyographic activity, mechanical power, and relaxation rates following inspiratory ribcage muscle fatigue.

Sci Rep 2021 06 14;11(1):12475. Epub 2021 Jun 14.

Dipartimento Di Elettronica, Informazione E Bioingegneria, Politecnico Di Milano, Milan, Italy.

Muscle fatigue is a complex phenomenon enclosing various mechanisms. Despite technological advances, these mechanisms are still not fully understood in vivo. Here, simultaneous measurements of pressure, volume, and ribcage inspiratory muscle activity were performed non-invasively during fatigue (inspiratory threshold valve set at 70% of maximal inspiratory pressure) and recovery to verify if inspiratory ribcage muscle fatigue (1) leads to slowing of contraction and relaxation properties of ribcage muscles and (2) alters median frequency and high-to-low frequency ratio (H/L). During the fatigue protocol, sternocleidomastoid showed the fastest decrease in median frequency and slowest decrease in H/L. Fatigue was also characterized by a reduction in the relative power of the high-frequency and increase of the low-frequency. During recovery, changes in mechanical power were due to changes in shortening velocity with long-lasting reduction in pressure generation, and slowing of relaxation [i.e., tau (τ), half-relaxation time (½RT), and maximum relaxation rate (MRR)] was observed with no significant changes in contractile properties. Recovery of median frequency was faster than H/L, and relaxation rates correlated with shortening velocity and mechanical power of inspiratory ribcage muscles; however, with different time courses. Time constant of the inspiratory ribcage muscles during fatigue and recovery is not uniform (i.e., different inspiratory muscles may have different underlying mechanisms of fatigue), and MRR, ½RT, and τ are not only useful predictors of inspiratory ribcage muscle recovery but may also share common underlying mechanisms with shortening velocity.
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http://dx.doi.org/10.1038/s41598-021-92060-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203654PMC
June 2021

Thoracoabdominal asynchrony and paradoxical motion in Duchenne muscular dystrophy and healthy subjects during cough: A case control study.

Pediatr Pulmonol 2021 Jul 18;56(7):2136-2145. Epub 2021 Apr 18.

Departamento de Fisioterapia, Pneumo CardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Empresa Brasileira de Serviços Hospitalares (EBSERH), Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brasil.

Objective: To assess thoracoabdominal asynchrony (TAA) and inspiratory paradoxical motion at different positionings in subjects with Duchenne muscular dystrophy (DMD) versus healthy subjects during quiet spontaneous breathing (QB) and cough.

Methods: This is a case control study with a matched-pair design. We assessed 14 DMD subjects and 12 controls using optoelectronic plethysmography (OEP) during QB and spontaneous cough in 3 positions: supine, supine with headrest raised at 45°, and sitting with back support at 80°. The TAA was assessed using phase angle (θ) between upper (RCp) and lower rib cage (RCa) and abdomen (AB), as well as the percentage of inspiratory time the RCp (IP ), RCa (IP ), and AB (IP ) moved in opposite directions.

Results: During cough, DMD group showed higher RCp and RCa θ (p < .05), RCp and AB θ (p < .05) in supine and 45° positions, and higher RCp and Rca θ (p = .006) only in supine position compared with controls. Regarding the intragroup analysis, during cough, DMD group presented higher RCp and AB θ (p = .02) and RCa and AB θ (p = .002) in supine and higher RCa and AB θ (p = .002) in 45° position when compared to 80°. Receiver operating characteristic curve analyzes were able to discriminate TAA between controls and DMD in RCa supine position (area under the curve: 0.81, sensibility: 78.6% and specificity: 91.7%, p = .001).

Conclusion: Subjects with DMD yields TAA with insufficient deflation of chest wall compartments and rib cage distortion during cough, by noninvasive assessment.
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http://dx.doi.org/10.1002/ppul.25412DOI Listing
July 2021

Respiratory muscle imaging by ultrasound and MRI in neuromuscular disorders.

Eur Respir J 2021 Apr 16. Epub 2021 Apr 16.

Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands

Respiratory muscle weakness is common in neuromuscular disorders and leads to significant respiratory difficulties. Therefore, reliable and easy assessment of respiratory muscle structure and function in neuromuscular disorders is crucial. In the last decade, ultrasound and MRI emerged as promising imaging techniques to assess respiratory muscle structure and function. Respiratory muscle imaging directly measures the respiratory muscles and, in contrast to pulmonary function testing, is independent of patient effort. This makes respiratory muscle imaging suitable to use as tool in clinical respiratory management and as outcome parameter in upcoming drug trials for neuromuscular disorders, particularly in children. In this narrative review, we discuss the latest studies and technological developments in imaging of the respiratory muscles by US and MR, and its clinical application and limitations. We aim to increase understanding of respiratory muscle imaging and facilitate its use as outcome measure in daily practice and clinical trials.
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http://dx.doi.org/10.1183/13993003.00137-2021DOI Listing
April 2021

Computational fluid dynamics of the airways after left-upper pulmonary lobectomy: A case study.

Int J Numer Method Biomed Eng 2021 Jul 18;37(7):e3462. Epub 2021 Jun 18.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.

Pulmonary lobectomy is the gold standard intervention for lung cancer removal and consists of the complete resection of the affected lung lobe, which, coupled with the re-adaptation of the remaining thoracic structures, decreases the postoperative pulmonary function of the patient. Current clinical practice, based on spirometry and cardiopulmonary exercise tests, does not consider local changes, providing an average at-the-mouth estimation of residual functionality. Computational Fluid Dynamics (CFD) has proved a valuable solution to obtain quantitative and local information about airways airflow dynamics. A CFD investigation was performed on the airway tree of a left-upper pulmonary lobectomy patient, to quantify the effects of the postoperative alterations. The patient-specific bronchial models were reconstructed from pre- and postoperative CT scans. A parametric laryngeal model was merged to the geometries to account for physiological-like inlet conditions. Numerical simulations were performed in Fluent. The postoperative configuration revealed fluid dynamic variations in terms of global velocity (+23%), wall pressure (+48%), and wall shear stress (+39%). Local flow disturbances emerged at the resection site: a high-velocity peak of 4.92 m/s was found at the left-lower lobe entrance, with a local increase of pressure at the suture zone (18 Pa). The magnitude of pressure and secondary flows increased in the trachea and flow dynamics variations were observed also in the contralateral lung, causing altered lobar ventilation. The results confirmed that CFD is a patient-specific approach for a quantitative evaluation of fluid dynamics parameters and local ventilation providing additional information with respect to current clinical approaches.
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http://dx.doi.org/10.1002/cnm.3462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365666PMC
July 2021

Detection and Classification of Bronchiectasis Through Convolutional Neural Networks.

J Thorac Imaging 2021 Mar 24. Epub 2021 Mar 24.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico Department of Pathophysiology and Transplantation, Università degli Studi di Milano Department of Radiology, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico Milan, University of Milan, Milan Department of Clinical Sciences, Section of Radiology, University of Parma, Parma Department of Radiology, ASST Lodi, Ospedale Maggiore di Lodi, Lodi, Italy.

Purpose: Bronchiectasis is a chronic disease characterized by an irreversible dilatation of bronchi leading to chronic infection, airway inflammation, and progressive lung damage. Three specific patterns of bronchiectasis are distinguished in clinical practice: cylindrical, varicose, and cystic. The predominance and the extension of the type of bronchiectasis provide important clinical information. However, characterization is often challenging and is subject to high interobserver variability. The aim of this study is to provide an automatic tool for the detection and classification of bronchiectasis through convolutional neural networks.

Materials And Methods: Two distinct approaches were adopted: (i) direct network performing a multilabel classification of 32×32 regions of interest (ROIs) into 4 classes: healthy, cylindrical, cystic, and varicose and (ii) a 2-network serial approach, where the first network performed a binary classification between normal tissue and bronchiectasis and the second one classified the ROIs containing abnormal bronchi into one of the 3 bronchiectasis typologies. Performances of the networks were compared with other architectures presented in the literature.

Results: Computed tomography from healthy individuals (n=9, age=47±6, FEV1%pred=109±17, FVC%pred=116±17) and bronchiectasis patients (n=21, age=59±15, FEV1%pred=74±25, FVC%pred=91±22) were collected. A total of 19,059 manually selected ROIs were used for training and testing. The serial approach provided the best results with an accuracy and F1 score average of 0.84, respectively. Slightly lower performances were observed for the direct network (accuracy=0.81 and F1 score average=0.82). On the test set, cylindrical bronchiectasis was the subtype classified with highest accuracy, while most of the misclassifications were related to the varicose pattern, mainly to the cylindrical class.

Conclusion: The developed networks accurately detect and classify bronchiectasis disease, allowing to collect quantitative information regarding the radiologic severity and the topographical distribution of bronchiectasis subtype.
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http://dx.doi.org/10.1097/RTI.0000000000000588DOI Listing
March 2021

Quantitative inspiratory-expiratory chest CT to evaluate pulmonary involvement in pediatric hematopoietic stem-cell transplantation patients.

Pediatr Pulmonol 2021 05 23;56(5):1026-1035. Epub 2020 Dec 23.

Center for Pulmonary Imaging Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Pulmonary complications following allogeneic hematopoietic stem-cell transplantation (HSCT) are a significant source of morbidity and complications may arise from a myriad of infectious and noninfectious sources. These complications may occur soon or many months post-transplantation and can have a broad range of outcomes. Surveillance for pulmonary involvement in the pediatric HSCT population can be challenging due to poor compliance with clinical pulmonary function testing, primarily spirometry, and there may be a role for clinical imaging to provide an additional means of monitoring, particularly in the era of clinical low-dose computed tomography (CT) protocols. In this single-site, retrospective study, a review of our institution's radiological and HSCT databases was conducted to assess the utility of a quantitative CT algorithm to describe ventilation abnormalities on high-resolution chest CT scans of pediatric HSCT patients. Thirteen non-contrast enhanced chest CT examinations acquired both in inspiration and expiration, from 12 deceased HSCT patients (median age at HSCT 10.4 years, median days of CT 162) were selected for the analysis. Also, seven age-matched healthy controls (median age 15.5) with non-contrast-enhanced inspiration-expiration chest CT were selected for comparison. We report that, compared to healthy age-matched controls, HSCT patients had larger percentages of poorly ventilated (median, 13.5% vs. 2.3%, p < .001) and air trapped (median 12.3% vs. 0%, p < .001) regions of lung tissue, suggesting its utility as a potential screening tool. Furthermore, there was wide variation within individual HSCT patients, supporting the use of multivolume CT and quantitative analysis to describe and phenotype post-transplantation lung involvement.
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http://dx.doi.org/10.1002/ppul.25223DOI Listing
May 2021

Longitudinal Assessment of Patients With Cystic Fibrosis Lung Disease With Multivolume Noncontrast MRI and Spirometry.

J Magn Reson Imaging 2021 05 10;53(5):1570-1580. Epub 2020 Dec 10.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Centro Fibrosi Cistica, Milan, Italy.

Background: MRI has been suggested as a radiation-free imaging modality to investigate early structural alterations and regional functional impairment in cystic fibrosis (CF) lung disease.

Purpose/hypothesis: To compare functional and morphological MRI changes over the course of the disease to changes in spirometry.

Study Type: Longitudinal retrospective study.

Population: Twenty patients with CF lung disease (at baseline, age = 16.5 (13.3-20.6) years, forced expiratory volume in 1 second (as % of predicted [%pred]) FEV = 71 (59-87) %pred, forced expiratory flow at 25-75% of forced vital capacity FEF = 39 (25-63) %pred.

Field Strength/sequence: 1.5T / T -weighted HASTE; T -weighted TSE-PROPELLER; T -weighted bSSFP; T -weighted 3D GRE.

Assessment: Nonenhanced chest MRI and spirometry were retrospectively collected over a 3-year period from the initial recruitment visit. Images acquired at end-inspiration and end-expiration were registered by software using the optical flow method to measure expiratory-inspiratory differences in MR signal-intensity (Δ H-MRI). Measures of CF functional impairment were defined from Δ H-MRI: Δ H-MRI median, Δ H-MRI quartile coefficient of variation (QCV), and percent low-signal-variation volume (LVV). MR images were also evaluated by three readers using a CF-specific scoring system.

Statistical Tests: Spearman correlation analysis, Spearman rank correlation analysis, linear mixed-effect model analysis, intraclass correlation coefficient.

Results: Functional imaging parameters and total morphological score correlated with all spirometric measures, as did subscores of bronchial wall thickening/bronchiectasis, mucus plugging, and consolidation. Overall, the percent change of Δ1H-MRI median correlated with the percent change of FEV (ΔFEV , r = 0.41, P < 0.01) and the percent change of FEF (ΔFEF25-75%, r = 0.38, P < 0.01). The percent change of LVV correlated with ΔFEV (r = -0.47, P < 0.001) and ΔFEF (r = -0.50, P < 0.001).

Data Conclusion: These preliminary results suggest that nonenhanced multivolume MRI may provide a feasible tool to regionally map early pulmonary alterations for longitudinal evaluation of CF lung disease, without exposing the patients to ionizing radiation.

Level Of Evidence: 3T TECHNICAL EFFICACY STAGE: 5.
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http://dx.doi.org/10.1002/jmri.27461DOI Listing
May 2021

Discharge ward during the SARS-CoV-2 pandemic: an effective way to increase patient turnover when human resources are scarce.

Infez Med 2020 Dec;28(4):539-544

Division of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili, Brescia, Italy.

During the SARS-CoV-2 pandemic, the province of Brescia (Italy) had a significant number of COVID-19 cases, which led to a subversion of the ordinary structure of the university hospital ASST Spedali Civili, driven by the need to hospitalize as many patients as possible in a narrow period of time. At the peak of the epidemic, a rapid hospitalization discharge area, the Discharge Ward (DW), was set up with the aim of facilitating the rapid turnover of patients in the wards where the most severe patients had to be hospitalized. The organization and activities carried out are described in the results of this reproducible experience during epidemic events.
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December 2020

Quantitative CT Analysis in Chronic Hypersensitivity Pneumonitis: A Convolutional Neural Network Approach.

Acad Radiol 2020 Nov 6. Epub 2020 Nov 6.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.

Rationale And Objectives: Chronic hypersensitivity pneumonitis (cHP) is a heterogeneous condition, where both small airway involvement and fibrosis may simultaneously occur. Computer-aided analysis of CT lung imaging is increasingly used to improve tissue characterization in interstitial lung diseases (ILD), quantifying disease extension, and progression. We aimed to quantify via a convolutional neural network (CNN) method the extent of different pathological classes in cHP, and to determine their correlation to pulmonary function tests (PFTs) and mosaic attenuation pattern.

Materials And Methods: The extension of six textural features, including consolidation (C), ground glass opacity (GGO), fibrosis (F), low attenuation areas (LAA), reticulation (R) and healthy regions (H), was quantified in 27 cHP patients (age: 56 ± 11.5 years, forced vital capacity [FVC]% = 57 ± 17) acquired at full-inspiration via HRCT. Each class extent was correlated to PFTs and to mosaic attenuation pattern.

Results: H showed a positive correlation with FVC%, FEV1% (forced expiratory volume), total lung capacity%, and diffusion of carbon monoxide (DLCO)% (r = 0.74, r = 0.78, r = 0.73, and r = 0.60, respectively, p < 0.001). GGO, R and C negatively correlated with FVC% and FEV1% with the highest correlations found for R (r = -0.44, and r = -0.46 respectively, p < 0.05); F negatively correlated with DLCO% (r = -0.42, p < 0.05). Patients with mosaic attenuation pattern had significantly more H (p = 0.04) and lower R (p = 0.02) and C (p = 0.0009) areas, and more preserved lung function indices (higher FVC%; p = 0.04 and DLCO%; p = 0.05), but did not show more air trapping in lung function tests.

Conclusion: CNN quantification of pathological tissue extent in cHP improves its characterization and shows correlation with PFTs. LAA can be overestimated by visual, qualitative CT assessment and mosaic attenuation pattern areas in cHP represents patchy ILD rather than small-airways disease.
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http://dx.doi.org/10.1016/j.acra.2020.10.009DOI Listing
November 2020

Quantitative Multivolume Proton-Magnetic Resonance Imaging in Lung Transplant Recipients: Comparison With Computed Tomography and Spirometry.

Acad Radiol 2021 Oct 9;28(10):e297-e305. Epub 2020 Jul 9.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.

Rationale And Objectives: Acute and chronic graft rejection remains the major problem in clinical surveillance of lung-transplanted patients and early detection of complications is of capital importance to allow the optimal therapeutic option. The aim of this study was to investigate the role of quantitative non contrast-enhanced magnetic resonance imaging (MRI) as a non-ionizing imaging modality to assess ventilation impairment in patients who have undergone lung transplantation, in comparison with quantitative computed tomography (CT) and spirometry.

Materials And Methods: Ten lung-transplanted patients (39 ±12 years, forced-expiratory volume in 1 second (FEV1) = 81 ± 27%, forced vital capacity (FVC) = 87 ± 27%) were acquired in breath-hold at full-expiration and full-inspiration with 1.5T MRI and CT. Maps of expiratory-inspiratory difference in MR signal-intensity and CT-density were computed to estimate regional ventilation. Based on expiratory, inspiratory, and expiratory-inspiratory difference values, each pixel was classified as healthy (H), low ventilation (LV), air trapping (AT), and consolidation (C) and the percent extent of each class was quantified.

Results: Overall, expiratory-inspiratory difference in MR signal-intensity correlated to CT-density (r = 0.64, p < 0.0001) and to FEV1 (ρ = 0.71, p = 0.02). The linear correlation between MRI and CT functional maps considering all the four classes is r = 0.93 (p < 0.0001). MRI percent volumes of H, AT, and C correlated to FEV1 %pred, with the highest correlation reported for AT (ρ = -0.82).

Conclusion: Results demonstrated a good agreement between MRI and CT ventilation imaging and between the corresponding percent volumes of lung damage. Quantitative MRI may represent an accurate non-ionizing imaging technique for longitudinal monitoring of lung transplant recipients.
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http://dx.doi.org/10.1016/j.acra.2020.05.026DOI Listing
October 2021

Simulation of bronchial airway acoustics in healthy and asthmatic subjects.

PLoS One 2020 10;15(2):e0228603. Epub 2020 Feb 10.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.

The onset and development of many airway pathologies affect sound propagation throughout the respiratory system; changes in respiratory sounds are detected primarily by auscultation, which is highly skill dependent. The aim of the present study was to compare healthy and asthmatic pulmonary acoustics by applying a 1D model of wave propagation on CT-based patient-specific geometries. High-resolution CT lung images were acquired in five healthy volunteers and five asthmatic patients at total lung capacity (TLC) and functional residual capacity (FRC). Tracheobronchial trees were reconstructed from CT images. Acoustic pressure, impedance and wall radial velocity were measured by simulating acoustic wave propagation of two external, acoustic pressure waves (1 Pa, 200 and 600 Hz) from the trachea level to the 4th generation. In asthmatic patients, acoustic pressure averaged across the last three generations showed a reduction equal to 29.7% (p<0.01) at FRC, at 200 Hz; input and terminal impedance were 34.5% (p<0.05) higher both at FRC and TLC; wall radial velocity was more than 80% (p<0.05) lower in higher generations both at FRC and TLC. Airway differences in asthma alter acoustic parameters at FRC and TLC, with the greatest difference at FRC and 200 Hz. Acoustic wave propagation analysis represents a quantitative approach that has potential to objectively characterize airway differences in individuals with diseases such as asthma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228603PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010248PMC
May 2020

Diaphragm Involvement in Duchenne Muscular Dystrophy (DMD): An MRI Study.

J Magn Reson Imaging 2020 02 13;51(2):461-471. Epub 2019 Jul 13.

The Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Italy.

Background: Duchenne muscular dystrophy (DMD) is characterized by progressive weakness and wasting of skeletal, cardiac, and respiratory muscles, with consequent cardiopulmonary failure as the main cause of death. Reliable outcome measures able to demonstrate specific trends over disease progression are essential.

Purpose: To investigate MRI as a noninvasive imaging modality to assess diaphragm impairment in DMD. In particular, we sought to correlate MRI measurement of diaphragm structure and function with pulmonary function tests and with the abdominal volumes (V ) measured by optoelectronic plethysmography, being an index of the action of the diaphragm.

Study Type: Cross-sectional study.

Population: Twenty-six DMD patients (17.9 ± 6.2 years) and 12 age-matched controls (17.8 ± 5.9 years).

Field Strength/sequence: 3-Point gradient echo Dixon sequence at 3T.

Assessment: Images were acquired in breath-hold at full-expiration (EXP) and full-inspiration (INSP). INSP and EXP lung volumes were segmented and the diaphragm surface was reconstructed as the bottom surface of the left and the right lung. The inspiratory and the expiratory diaphragm surfaces were aligned by a nonrigid iterative closest point algorithm. On MRI we measured: 1) craniocaudal diaphragmatic excursion; 2) diaphragm fatty infiltration.

Statistical Tests: Three-parameter sigmoid regression, one-way analysis of variance (ANOVA), Spearman's correlation.

Results: In patients, diaphragm excursion decreased with age (r = 0.68, P < 0.0001) and fat fraction increased (r = 0.51, P = 0.0002). In healthy subjects, diaphragm excursion and fat fraction had no relationship with age. Diaphragm excursion decreased with decreasing FEV %pred (r = 0.78, P < 0.0001) and FVC %pred (r = 0.76, P < 0.0001) and correlated with V (r = 0.60, P = 0.0002). Fatty infiltration increased with decreasing FEV1 %pred (r = -0.88, P < 0.0001) and FVC %pred (r = -0.88, P < 0.0001).

Data Conclusion: The progressive structural and functional diaphragm impairment is highly related to pulmonary function tests and to V . The results suggest that MRI might represent a new and noninvasive tool for the functional and structural assessment of the diaphragm.

Level Of Evidence: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:461-471.
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http://dx.doi.org/10.1002/jmri.26864DOI Listing
February 2020

The effect of primary graft dysfunction after lung transplantation on parenchymal remodeling detected by quantitative computed tomography.

J Thorac Dis 2019 Apr;11(4):1213-1222

Unità Operativa di Chirurgia Toracica e dei Trapianti di Polmone, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico di Milano, Milano, Italy.

Background: Regional analysis by computed tomography (CT) is an attractive technique to interpret lung patterns after transplantation (LTx). We evaluated the application of CT functional mask derived parameters to determine whether development of primary graft dysfunction (PGD) is associated with short and/or long-term postoperative evidences of pulmonary function alterations.

Methods: A total of 38 patients who underwent bilateral LTx were evaluated at 24, 48 and 72 hours after the end of surgery to establish PGD occurrence and grading. CT scans at 3 and 12 months after LTx were analyzed to measure specific gas volume (SV) changes normalized on expiratory SVgEXP of the whole lung (ΔSV/SV) and to obtain functional masks of density variation, namely maps of low ventilation (LV), consolidation (C), air trapping (AT) and healthy parenchyma (H).

Results: Our main result was the evidence of a marked decrease in ΔSV/SV in all subjects, irrespectively on PGD, at each time point after LTx, indicating a high degree of ventilation defects versus healthy. High percentages of LV were found in all subjects while percentages of AT and C were negligible.

Conclusions: We demonstrate that quantification of ventilation defects by CT functional mask offers insights into the correlation between PGD and pulmonary function after LTx at short and mid-term.
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http://dx.doi.org/10.21037/jtd.2019.04.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531734PMC
April 2019

Quantitative multivolume proton-magnetic resonance imaging in patients with cystic fibrosis lung disease: comparison with clinical indicators.

Eur Respir J 2019 05 2;53(5). Epub 2019 May 2.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.

This cross-sectional study aims to verify the relationship between quantitative multivolume proton-magnetic resonance imaging (H-MRI) and clinical indicators of ventilatory abnormalities in cystic fibrosis (CF) lung disease.Non-enhanced chest MRI, spirometry and multiple breath washout was performed by 28 patients (10-27 years) with CF lung disease. Images acquired at end-inspiration and end-expiration were registered by optical flow to estimate expiratory-inspiratory proton-density change (ΔH-MRI) as a measure of regional ventilation. Magnetic resonance images were also evaluated using a CF-specific scoring system.Biomarkers of CF ventilation impairment were defined from the ΔH-MRI as follows: ΔH-MRI median, ΔH-MRI quartile coefficient of variation (QCV) and percentage of low-ventilation volume (%LVV). Imaging biomarkers correlated to all the clinical measures of ventilation abnormality, with the strongest correlation between ΔH-MRI median and forced expiratory volume in 1 s (r=0.44, p<0.001), ΔH-MRI QCV and lung clearance index (LCI) (r=0.51, p<0.001) and %LVV and LCI (r=0.66, p<0.001). Correlations were also found between imaging biomarkers of ventilation and morphological scoring.The study showed a significant correlation between quantitative multivolume MRI and clinical indicators of CF lung disease. MRI, as a non-ionising imaging technique, may be particularly attractive in CF care for longitudinal evaluation, providing a new imaging biomarker to detect early ventilatory abnormalities.
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http://dx.doi.org/10.1183/13993003.02020-2017DOI Listing
May 2019

Technical challenges of quantitative chest MRI data analysis in a large cohort pediatric study.

Eur Radiol 2019 Jun 5;29(6):2770-2782. Epub 2018 Dec 5.

Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.

Objectives: This study was conducted in order to evaluate the effect of geometric distortion (GD) on MRI lung volume quantification and evaluate available manual, semi-automated, and fully automated methods for lung segmentation.

Methods: A phantom was scanned with MRI and CT. GD was quantified as the difference in phantom's volume between MRI and CT, with CT as gold standard. Dice scores were used to measure overlap in shapes. Furthermore, 11 subjects from a prospective population-based cohort study each underwent four chest MRI acquisitions. The resulting 44 MRI scans with 2D and 3D Gradwarp were used to test five segmentation methods. Intraclass correlation coefficient, Bland-Altman plots, Wilcoxon, Mann-Whitney U, and paired t tests were used for statistics.

Results: Using phantoms, volume differences between CT and MRI varied according to MRI positions and 2D and 3D Gradwarp correction. With the phantom located at the isocenter, MRI overestimated the volume relative to CT by 5.56 ± 1.16 to 6.99 ± 0.22% with body and torso coils, respectively. Higher Dice scores and smaller intraobject differences were found for 3D Gradwarp MR images. In subjects, semi-automated and fully automated segmentation tools showed high agreement with manual segmentations (ICC = 0.971-0.993 for end-inspiratory scans; ICC = 0.992-0.995 for end-expiratory scans). Manual segmentation time per scan was approximately 3-4 h and 2-3 min for fully automated methods.

Conclusions: Volume overestimation of MRI due to GD can be quantified. Semi-automated and fully automated segmentation methods allow accurate, reproducible, and fast lung volume quantification. Chest MRI can be a valid radiation-free imaging modality for lung segmentation and volume quantification in large cohort studies.

Key Points: • Geometric distortion varies according to MRI setting and patient positioning. • Automated segmentation methods allow fast and accurate lung volume quantification. • MRI is a valid radiation-free alternative to CT for quantitative data analysis.
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http://dx.doi.org/10.1007/s00330-018-5863-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510873PMC
June 2019

Mechanisms of exercise limitation in patients with chronic hypersensitivity pneumonitis.

ERJ Open Res 2018 Jul 22;4(3). Epub 2018 Aug 22.

Divisao de Pneumologia, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sâo Paulo, Sâo Paulo, Brazil.

Small airway and interstitial pulmonary involvements are prominent in chronic hypersensitivity pneumonitis (cHP). However, their roles on exercise limitation and the relationship with functional lung tests have not been studied in detail. Our aim was to evaluate exercise performance and its determinants in cHP. We evaluated maximal cardiopulmonary exercise testing performance in 28 cHP patients (forced vital capacity 57±17% pred) and 18 healthy controls during cycling. Patients had reduced exercise performance with lower peak oxygen production (16.6 (12.3-19.98) mL·kg·min 25.1 (16.9-32.0), p=0.003), diminished breathing reserve (% maximal voluntary ventilation) (12 (6.4-34.8)% 41 (32.7-50.8)%, p<0.001) and hyperventilation (minute ventilation/carbon dioxide production slope 37±5 31±4, p<0.001). All patients presented oxygen desaturation and augmented Borg dyspnoea scores (8 (5-10) 4 (1-7), p=0.004). The prevalence of dynamic hyperinflation was found in only 18% of patients. When comparing cHP patients with normal and low peak oxygen production (<84% pred, lower limit of normal), the latter exhibited a higher minute ventilation/carbon dioxide production slope (39±5.0 34±3.6, p=0.004), lower tidal volume (0.84 (0.78-0.90) L 1.15 (0.97-1.67) L, p=0.002), and poorer physical functioning score on the Short form-36 health survey. Receiver operating characteristic curve analysis showed that reduced lung volumes (forced vital capacity %, total lung capacity % and diffusing capacity of the lung for carbon dioxide %) were high predictors of poor exercise capacity. Reduced exercise capacity was prevalent in patients because of ventilatory limitation and not due to dynamic hyperinflation. Reduced lung volumes were reliable predictors of lower performance during exercise.
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http://dx.doi.org/10.1183/23120541.00043-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104296PMC
July 2018

Multiparametric Analysis of Sniff Nasal Inspiratory Pressure Test in Middle Stage Amyotrophic Lateral Sclerosis.

Front Neurol 2018 2;9:306. Epub 2018 May 2.

PneumoCardioVascular Laboratory, Hospital Universitário Onofre Lopes, Empresa Brasileira de Serviços Hospitalares (EBSERH), Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte, Natal, Brazil.

The relaxation rates and contractile properties of inspiratory muscles are altered with inspiratory muscle weakness and fatigue. This fact plays an important role in neuromuscular disorders patients and had never been extensively studied in amyotrophic lateral sclerosis (ALS). In this cross-sectional study, these parameters were investigated non-invasively through nasal inspiratory sniff pressure test (SNIP) in 39 middle stage spinal onset ALS subjects and compared with 39 healthy controls. ALS patients were also divided into three subgroups according to a decline in their percentage of predicted forced vital capacity (FVC) as well as a decline in the ALS functional rating scale score and its respiratory subscore (R-subscore) in order to determine the best parameter linked to early respiratory muscle weakness. When compared with healthy subjects, middle stage ALS subjects exhibited a significantly lower ( < 0.0001) maximum relaxation rate and maximum rate of pressure development (MRPD), as well as a significantly higher ( < 0.0001) tau (τ), contraction time, and half-relaxation time. The results from receiver operating characteristic curves showed that MRPD (AUC 0.735,  < 0.001) and FVC (AUC 0.749,  = 0.009) were the best discriminator parameters between ALS patients with ≤30 and >30 points in the ALS functional rating scale. In addition, 1/2RT (AUC 0.720,  = 0.01), FVC (AUC 0.700,  = 0.03), τ (AUC 0.824,  < 0.0001), and MRPD (AUC 0.721,  = 0.01) were the parameters more sensitive in detecting a fall of three points in the R-subscore. On the other hand, MRPD (AUC 0.781,  < 0.001), τ (AUC 0.794,  = 0.0001), and percentage of predicted of SNIP (AUC 0.769,  = 0.002) were the parameters able to detect a fall in 30% of the FVC in middle stage ALS patients. The contractile properties and relaxation rates of the diaphragm are altered in middle stage spinal onset ALS when compared with healthy subjects. These parameters are able to discriminate between those middle stage ALS subjects with early decline in inspiratory muscle function and those who not.
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http://dx.doi.org/10.3389/fneur.2018.00306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940741PMC
May 2018

Assessment of pulmonary structure-function relationships in young children and adolescents with cystic fibrosis by multivolume proton-MRI and CT.

J Magn Reson Imaging 2018 08 19;48(2):531-542. Epub 2018 Feb 19.

Center for Pulmonary Imaging Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Background: Lung disease is the most frequent cause of morbidity and mortality in patients with cystic fibrosis (CF), and there is a shortage of sensitive biomarkers able to regionally monitor disease progression and to assess early responses to therapy.

Purpose: To determine the feasibility of noncontrast-enhanced multivolume MRI, which assesses intensity changes between expiratory and inspiratory breath-hold images, to detect and quantify regional ventilation abnormalities in CF lung disease, with a focus on the structure-function relationship.

Study Type: Retrospective.

Population: Twenty-nine subjects, including healthy young children (n = 9, 7-37 months), healthy adolescents (n = 4, 14-22 years), young children with CF lung disease (n = 10, 7-47 months), and adolescents with CF lung disease (n = 6, 8-18 years) were studied.

Field Strength/sequence: 3D spoiled gradient-recalled sequence at 1.5T.

Assessment: Subjects were scanned during breath-hold at functional residual capacity (FRC) and total lung capacity (TLC) through noncontrast-enhanced MRI and CT. Expiratory-inspiratory differences in MR signal-intensity (Δ H-MRI) and CT-density (ΔHU) were computed to estimate regional ventilation. MR and CT images were also evaluated using a CF-specific scoring system.

Statistical Tests: Quadratic regression, Spearman's correlation, one-way analysis of variance (ANOVA).

Results: Δ H-MRI maps were sensitive to ventilation heterogeneity related to gravity dependence in healthy lung and to ventilation impairment in CF lung disease. A high correlation was found between MRI and CT ventilation maps (R  = 0.79, P < 0.001). Globally, Δ H-MRI and ΔHU decrease with increasing morphological score (respectively, R  = 0.56, P < 0.001 and R  = 0.31, P < 0.001). Locally, Δ H-MRI was higher in healthy regions (median 15%) compared to regions with bronchiectasis, air trapping, consolidation, and to segments fed by airways with bronchial wall thickening (P < 0.001).

Data Conclusion: Multivolume noncontrast-enhanced MRI, as a nonionizing imaging modality that can be used on nearly any MRI scanner without specialized equipment or gaseous tracers, may be particularly valuable in CF care, providing a new imaging biomarker to detect early alterations in regional lung structure-function.

Level Of Evidence: 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:531-542.
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http://dx.doi.org/10.1002/jmri.25978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098984PMC
August 2018

Computed tomography in hypersensitivity pneumonitis: main findings, differential diagnosis and pitfalls.

Expert Rev Respir Med 2018 01 26;12(1):5-13. Epub 2017 Oct 26.

a Pulmonary Division, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina , Universidade de Sao Paulo , Sao Paulo , Brazil.

Introduction: Hypersensitivity pneumonitis (HP) is a disease with variable clinical presentation in which inflammation in the lung parenchyma is caused by the inhalation of specific organic antigens or low molecular weight substances in genetically susceptible individuals. Alterations of the acute, subacute and chronic forms may eventually overlap, and the diagnosis based on temporality and presence of fibrosis (acute/inflammatory HP vs. chronic HP) seems to be more feasible and useful in clinical practice. Differential diagnosis of chronic HP with other interstitial fibrotic diseases is challenging due to the overlap of the clinical history, and the functional and imaging findings of these pathologies in the terminal stages. Areas covered: This article reviews the essential features of HP with emphasis on imaging features. Moreover, the main methodological limitations of high-resolution computed tomography (HRCT) interpretation are discussed, as well as new perspectives with volumetric quantitative CT analysis as a useful tool for retrieving detailed and accurate information from the lung parenchyma. Expert commentary: Mosaic attenuation is a prominent feature of this disease, but air trapping in chronic HP seems overestimated. Quantitative analysis has the potential to estimate the involvement of the pulmonary parenchyma more accurately and could correlate better with pulmonary function results.
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http://dx.doi.org/10.1080/17476348.2018.1395282DOI Listing
January 2018

Comparison between multivolume CT-based surrogates of regional ventilation in healthy subjects.

Acad Radiol 2014 Oct 7;21(10):1268-75. Epub 2014 Aug 7.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, P.zza L. da Vinci, 32, 20133 Milano, Italy. Electronic address:

Rationale And Objectives: The assessment of regional ventilation is of critical importance when investigating lung function during disease progression and planning of pulmonary interventions. Recently, different computed tomography (CT)-based parameters have been proposed as surrogates of lung ventilation. The aim of the present study was to compare these parameters, namely variations of density (ΔHU), specific volume (sVol), and specific gas volume (ΔSVg) between different lung volumes, in relation to their topographic distribution within the lung.

Materials And Methods: Ten healthy volunteers were scanned via high-resolution CT at residual volume (RV) and total lung capacity (TLC); ΔHU, sVol, and ΔSVg were mapped voxel by voxel after registering TLC onto RV. Variations of the three parameters along the vertical and horizontal directions were analyzed.

Results: Along the vertical direction (from ventral to dorsal regions), a strong dependence on gravity was found in ΔHU and sVol, with greater values in the dorsal regions of the lung (P < .001), whereas ΔSVg was more homogeneously distributed within the lung. Conversely, along the caudocranial direction (from lung bases to apexes) where no gravitational gradient is present, the three parameters behaved similarly, with lower values at the apices.

Conclusions: ΔHU, sVol, and ΔSVg behave differently along the gravity direction. As the greater amount of air delivered to the dependent portion of the lung supplies a larger number of alveoli, the amount of gas delivered to alveoli compared to the mass of tissue is not gravity dependent. The minimization of gravity dependence in the distribution of ventilation when using ΔSVg suggests that this parameter is more reliable to discriminate healthy from pathologic regions.
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http://dx.doi.org/10.1016/j.acra.2014.05.022DOI Listing
October 2014

Assessment of regional lung function with multivolume (1)H MR imaging in health and obstructive lung disease: comparison with (3)He MR imaging.

Radiology 2014 Nov 15;273(2):580-90. Epub 2014 Jun 15.

From the Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Piazza L. da Vinci 32, 20133 Milan, Italy (F.P., A.A.); Mallinckrodt Institute of Radiology (J.D.Q., D.A.Y.), Department of Internal Medicine (M.C.), and Department of Physics (J.C.W.), Washington University School of Medicine, St Louis, Mo; and Center for Pulmonary Imaging Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio (J.C.W.).

Purpose: To introduce a method based on multivolume proton (hydrogen [(1)H]) magnetic resonance (MR) imaging for the regional assessment of lung ventilatory function, investigating its use in healthy volunteers and patients with obstructive lung disease and comparing the outcome with the outcome of the research standard helium 3 ((3)He) MR imaging.

Materials And Methods: The institutional review board approved the HIPAA-compliant protocol, and informed written consent was obtained from each subject. Twenty-six subjects, including healthy volunteers (n = 6) and patients with severe asthma (n = 11) and mild (n = 6) and severe (n = 3) emphysema, were imaged with a 1.5-T whole-body MR unit at four lung volumes (residual volume [ RV residual volume ], functional residual capacity [ FRC functional residual capacity ], 1 L above FRC functional residual capacity [ FRC+1 L 1 L above FRC ], total lung capacity [ TLC total lung capacity ]) with breath holds of 10-11 seconds, by using volumetric interpolated breath-hold examination. Each pair of volumes were registered, resulting in maps of (1)H signal change between the two lung volumes. (3)He MR imaging was performed at FRC+1 L 1 L above FRC by using a two-dimensional gradient-echo sequence. (1)H signal change and (3)He signal were measured and compared in corresponding regions of interest selected in ventral, intermediate, and dorsal areas.

Results: In all volunteers and patients combined, proton signal difference between TLC total lung capacity and RV residual volume correlated positively with (3)He signal (correlation coefficient R(2) = 0.64, P < .001). Lower (P < .001) but positive correlation results from (1)H signal difference between FRC functional residual capacity and FRC+1 L 1 L above FRC (R(2) = 0.44, P < .001). In healthy volunteers, (1)H signal changes show a higher median and interquartile range compared with patients with obstructive disease and significant differences between nondependent and dependent regions.

Conclusion: Findings in this study demonstrate that multivolume (1)H MR imaging, without contrast material, can be used as a biomarker for regional ventilation, both in healthy volunteers and patients with obstructive lung disease.
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http://dx.doi.org/10.1148/radiol.14132470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334302PMC
November 2014

Regional lung function and heterogeneity of specific gas volume in healthy and emphysematous subjects.

Eur Respir J 2013 May 9;41(5):1179-88. Epub 2012 Aug 9.

TBMLab Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.

The aim of our study was to study regional lung function by standard computed tomography (CT) and characterise regional variations of density and specific gas volume (SVg) between different lung volumes. We studied 10 healthy and 10 severely emphysematous subjects. Corresponding CT images taken at high and low lung volumes were registered by optical flow to obtain two-dimensional maps of pixel-by-pixel differences of density (ΔHU) and SVg (ΔSVg) at slice levels near the aortic arch, carina and top diaphragm. In healthy subjects, ΔHU was higher at all levels (p<0.001) with higher variability expressed as interquartile range (p<0.001), largely due to its differences between dorsal and ventral regions. In patients, median ΔSVg values were 3.2 times lower than healthy volunteers (p<0.001), while heterogeneity of ΔSVg maps, expressed as quartile coefficient of variation, was 5.4 times higher (p<0.001). In all patients, there were areas with negative values of ΔSVg. In conclusion, ΔSVg is uniform in healthy lungs and minimally influenced by gravity. The significant ΔSVg heterogeneity observed in emphysema allows identification of areas of alveolar destruction and gas trapping and suggests that ΔSVg maps provide useful information for evaluation and planning of emerging treatments that target trapped gas for removal.
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http://dx.doi.org/10.1183/09031936.00050112DOI Listing
May 2013
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