Treatment of Advanced Emphysema with Emphysematous Lung Sealant (AeriSeal (R))

Background: This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. Objectives: The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. Methods: ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2-4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. Results: Treatment was well tolerated. There were no treatment-related deaths (i.e. within 90 days of treatment), and an acceptable short-and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients {[}n = 14; change in residual volume/total lung capacity (Delta RV/TLC) = -7.4 +/- 10.3%; Delta forced expiratory volume in 1 s (Delta FEV(1)) = +15.9 +/- 22.6%; change in forced vital capacity (Delta FVC) = +24.1 +/- 22.7%; change in carbon monoxide lung diffusion capacity (Delta DLCO) = +19.3 +/- 34.8%; change in 6-min walk test (Delta 6MWD) = +28.7 +/- 59.6 m; change in Medical Research Council Dyspnea (Delta MRCD) score = -1.0 +/- 1.04 units; change in St. George's Respiratory Questionnaire (Delta SGRQ) score = -9.9 +/- 15.3 units] than for GOLD stage IV patients (n = 7; Delta RV/TLC = -0.5 +/- 6.4%; Delta FEV 1 = +2.3 +/- 12.3%; Delta FVC = +2.6 +/- 21.1%; Delta DLCO = -2.8 +/- 17.2%; Delta 6MWD = +28.3 +/- 58.4 m; Delta MRCD = 0.3 +/- 0.81 units; Delta SGRQ = -6.7 +/- 7.0 units). Conclusions: ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted. Copyright (C) 2011 S. Karger AG, Base

Sparsity Regularization for Image Reconstruction with Poisson Data

This work investigates three penalized-likelihood expectation maximization (EM) algorithms for image reconstruction with Poisson data where the images are known a priori to be sparse in the space domain. The penalty functions considered are the 1 norm, the 0 “norm,” and a penalty function based on the sum of logarithms of pixel values, R(x) = np j=1 log xj ? + 1 . Our results show that the 1 penalized algorithm reconstructs scaled versions of the maximum-likelihood (ML) solution, which does not improve the sparsity over the traditional ML estimate. Due to the singularity of the Poisson log-likelihood at zero, the 0 penalized EM algorithm is equivalent to the maximum-likelihood EM algorithm. We demonstrate that the penalty based on the sum of logarithms produces sparser images than the ML solution. We evaluated these algorithms using experimental data from a position-sensitive Compton-imaging detector, where the spatial distribution of photon-emitters is known to be sparse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85938/1/Fessler235.pd

Regularized Image Reconstruction Algorithms for Dual-Isotope Myocardial Perfusion SPECT (MPS) Imaging Using a Cross-Tracer Prior

In simultaneous dual-isotope myocardial perfusion SPECT (MPS) imaging, data are simultaneously acquired to determine the distributions of two radioactive isotopes. The goal of this work was to develop penalized maximum likelihood (PML) algorithms for a novel cross-tracer prior that exploits the fact that the two images reconstructed from simultaneous dual-isotope MPS projection data are perfectly registered in space. We first formulated the simultaneous dual-isotope MPS reconstruction problem as a joint estimation problem. A cross-tracer prior that couples voxel values on both images was then proposed. We developed an iterative algorithm to reconstruct the MPS images that converges to the maximum a posteriori solution for this prior based on separable surrogate functions. To accelerate the convergence, we developed a fast algorithm for the cross-tracer prior based on the complete data OS-EM (COSEM) framework. The proposed algorithm was compared qualitatively and quantitatively to a single-tracer version of the prior that did not include the cross-tracer term. Quantitative evaluations included comparisons of mean and standard deviation images as well as assessment of image fidelity using the mean square error. We also evaluated the cross tracer prior using a three-class observer study with respect to the three-class MPS diagnostic task, i.e., classifying patients as having either no defect, reversible defect, or fixed defects. For this study, a comparison with conventional ordered subsets-expectation maximization (OS-EM) reconstruction with postfiltering was performed. The comparisons to the single-tracer prior demonstrated similar resolution for areas of the image with large intensity changes and reduced noise in uniform regions. The cross-tracer prior was also superior to the single-tracer version in terms of restoring image fidelity. Results of the three-class observer study showed that the proposed cross-tracer prior and the convergent algorithms improved the ima- - ge quality of dual-isotope MPS images compared to OS-EM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85873/1/Fessler3.pd

Benefits of Position–Sensitive Detectors for Source Detection with Known Background

We address the question of whether or not the directional or imaging information offered by a position-sensitive gamma-ray detector improves the detection accuracy when searching for a source of known shape amid a background of known intensity. We formulate the detection problem as a composite hypothesis testing problem and examine the behavior of the generalized likelihood ratio test (GLRT) in terms of the area under the receiver operating characteristic (AUC). Due to the analytical complexity of the GLRT in this case, we examine its asymptotic properties when the number of detected photons is large. We find that a detector of uniform sensitivity can more accurately detect a source when imaging information is used.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85968/1/Fessler245.pd

Benefits of Position-Sensitive Detectors for Radioactive Source Detection

There are many systems for counting photons such as gamma-rays emitted from radioactive sources. Many of these systems are also position-sensitive, which means that the system provides directional information about recorded events. This paper investigates whether or not the additional information provided by position-sensitive capability improves the performance of detecting a point-source in background. We analyze the asymptotic performance of the generalized likelihood ratio test (GLRT) and a test based on the maximum-likelihood (ML) estimate of the source intensity for systems with and without position-sensitive capability. When the background intensity is known and detector sensitivity is spatially uniform, we prove that position-sensitive capability increases the area under the receiver operating characteristic curve (AUC). For cases when detector sensitivity is nonuniform or background intensity is unknown, we provide numerical results to illustrate the effect of the parameters on detection performance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85967/1/Fessler6.pd

Hemodynamic effects of lung recruitment maneuvers in acute respiratory distress syndrome

Background: Clinical trials have, so far, failed to establish clear beneficial outcomes of recruitment maneuvers (RMs) on patient mortality in acute respiratory distress syndrome (ARDS), and the effects of RMs on the cardiovascular system remain poorly understood. Methods: A computational model with highly integrated pulmonary and cardiovascular systems was configured to replicate static and dynamic cardio-pulmonary data from clinical trials. Recruitment maneuvers (RMs) were executed in 23 individual in-silico patients with varying levels of ARDS severity and initial cardiac output. Multiple clinical variables were recorded and analyzed, including arterial oxygenation, cardiac output, peripheral oxygen delivery and alveolar strain. Results: The maximal recruitment strategy (MRS) maneuver, which implements gradual increments of positive end expiratory pressure (PEEP) followed by PEEP titration, produced improvements in PF ratio, carbon dioxide elimination and dynamic strain in all 23 in-silico patients considered. Reduced cardiac output in the moderate and mild in silico ARDS patients produced significant drops in oxygen delivery during the RM (average decrease of 423 ml min-1 and 526 ml min-1, respectively). In the in-silico patients with severe ARDS, however, significantly improved gas-exchange led to an average increase of 89 ml min-1 in oxygen delivery during the RM, despite a simultaneous fall in cardiac output of more than 3 l min-1 on average. Post RM increases in oxygen delivery were observed only for the in silico patients with severe ARDS. In patients with high baseline cardiac outputs (>6.5 l min-1), oxygen delivery never fell below 700 ml min-1. Conclusions: Our results support the hypothesis that patients with severe ARDS and significant numbers of alveolar units available for recruitment may benefit more from RMs. Our results also indicate that a higher than normal initial cardiac output may provide protection against the potentially negative effects of high intrathoracic pressures associated with RMs on cardiac function. Results from in silico patients with mild or moderate ARDS suggest that the detrimental effects of RMs on cardiac output can potentially outweigh the positive effects of alveolar recruitment on oxygenation, resulting in overall reductions in tissue oxygen delivery

Use of endobronchial one-way valves reveals questions on etiology of spontaneous pneumothorax: report of three cases

Spontaneous pneumothoraces are believed to arise when air from the supplying airway exit via a ruptured visceral pleural bleb into the pleural cavity. Endobronchial one-way valves (EBVs) allow air exit (but not entry) from individual segmental airways. Systematic deployment of EBVs was applied to three patients with secondary spontaneous pneumothoraces and persistent airleak. In all cases, balloon-catheter occlusion of the upper lobe bronchus stopped the airleak. EBVs applied to individual upper lobe segmental airways failed to terminate the airleak, which only stopped after placements of multiple EBVs to occlude all upper lobe segments. The observation questions the traditional belief of 'one-airway-one-bleb-one-leak' in spontaneous pneumothorax