Project description:PurposeThe computed tomography (CT)-derived ventilation imaging methodology employs deformable image registration (DIR) to recover respiratory motion-induced volume changes from an inhale/exhale CT image pair, as a surrogate for ventilation. The Integrated Jacobian Formulation (IJF) and Mass Conserving Volume Change (MCVC) numerical methods for volume change estimation represent two classes of ventilation methods, namely transformation based and intensity (Hounsfield Unit) based, respectively. Both the IJF and MCVC methods utilize subregional volume change measurements that satisfy a specified uncertainty tolerance. In previous publications, the ventilation images resulting from this numerical strategy demonstrated robustness to DIR variations. However, the reduced measurement uncertainty comes at the expense of measurement resolution. The purpose of this study was to examine the spatial correlation between robust CT-ventilation images and single photon emission CT-ventilation (SPECT-V).MethodsPreviously described implementations of IJF and MCVC require the solution of a large scale, constrained linear least squares problem defined by a series of robust subregional volume change measurements. We introduce a simpler parameterized implementation that reduces the number of unknowns while increasing the number of data points in the resulting least squares problem. A parameter sweep of the measurement uncertainty tolerance, τ , was conducted using the 4DCT and SPECT-V images acquired for 15 non-small cell lung cancer patients prior to radiotherapy. For each test case, MCVC and IJF CT-ventilation images were created for 30 different uncertainty parameter values, uniformly sampled from the range 0.01,0.25 . Voxel-wise Spearman correlation between the SPECT-V and the resulting CT-ventilation images was computed.ResultsThe median correlations between MCVC and SPECT-V ranged from 0.20 to 0.48 across the parameter sweep, while the median correlations for IJF and SPECT-V ranged between 0.79 and 0.82. For the optimal IJF tolerance τ=0.07 , the IJF and SPECT-V correlations across all 15 test cases ranged between 0.12 and 0.90. For the optimal MCVC tolerance τ=0.03 , the MCVC and SPECT-V correlations across all 15 test cases ranged between -0.06 and 0.84.ConclusionThe reported correlations indicate that robust methods generate ventilation images that are spatially consistent with SPECT-V, with the transformation-based IJF method yielding higher correlations than those previously reported in the literature. For both methods, overall correlations were found to marginally vary for τ∈[0.03,0.15] , indicating that the clinical utility of both methods is robust to both uncertainty tolerance and DIR solution.

Project description:PurposePatients with esophageal cancer treated with chemoradiation and surgery can develop pulmonary complications. Four-dimensional computed tomography-ventilation (4DCT-ventilation) is a developing imaging modality that uses 4DCT data to calculate lung ventilation. 4DCT-ventilation has been studied in the lung-cancer population but has yet to be extended to patients with esophageal cancer. The purpose of this study was to characterize 4DCT-ventilation-based spatial lung function for patients with esophageal cancer.Methods and materialsThirty-five patients with esophageal cancer who underwent 4DCT scans participated in the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging and a density change-based algorithm. To assess each patient's ventilation profile, radiologist interpretations and quantitative metrics were used. A radiologist interpreted the 4DCT-ventilation images for lobar-based defects and gravity-dependent atelectasis. The 4DCT-ventilation maps were reduced to single metrics intended to reflect the degree of ventilation heterogeneity. The quantitative metrics included the coefficient of variation and metrics based on the ventilation in each lung and each lung third (superior-inferior ventilation [Vent-SI] and anteroposterior ventilation). The functional profile of patients with esophageal cancer was characterized and compared (using the Mann-Whitney test) for cohorts based on thoracic comorbidities and radiologist-identified defects.ResultsRadiologist observations revealed that 26% of patients with esophageal cancer had lobar-based defects and 46% had gravity-dependent atelectasis. The baseline values were 0.52 ± 0.20 (mean ± SD), 11.2 ± 12.5, and 72.5 ± 14.6 for the coefficient of variation, the ventilation ratio of right to left lung, and Vent-SI metrics, respectively. The Vent-SI values were significantly different between patients with and without thoracic comorbidities (P = .05), and the anteroposterior ventilation metric was able to delineate patients with and without gravity-dependent atelectasis (P < .01).ConclusionsOur data demonstrate that approximately 30% of patients with esophageal cancer have significant ventilation heterogeneities. The current work uses radiologist observations and quantitative metrics to characterize 4DCT ventilation-based lung function for patients with esophageal cancer and presents data that can be used for future applications of 4DCT-ventilation to reduce thoracic toxicity for patients with esophageal cancer.

Project description:ObjectiveCurrent ventilation and perfusion dose-response studies focus on single-modalities (ventilation or perfusion) and perform pulmonary-toxicity assessment related to radiotherapy on a population-based basis. This study aims at quantitative and clinical evaluation of intrapatient differences between ventilation and perfusion dose-responses among lung cancer patients treated with radiotherapy.Methods20 patients enrolled on a prospective functional avoidance protocol underwent single photon emission computed tomography-CT ventilation and perfusion scans pre- and post-radiotherapy. Relative changes in pre- to post-treatment ventilation and perfusion in lung regions receiving ≥20 Gy were calculated. In addition, the slopes of the linear fit to the relative ventilation and perfusion changes in regions receiving 0-60 Gy were calculated. A radiologist read and assigned a functional defect score to pre- and post-treatment ventilation/perfusion scans.Results25% of patients had a difference >35% between ventilation and perfusion pre- to post-treatment changes and 20-30% of patients had opposite directions for ventilation and perfusion pre- to post-treatment changes. Using a semi-quantitative scale, radiologist assessment showed that 20% of patients had different pre- to post-treatment ventilation changes when compared to pre- to post-treatment perfusion changes.ConclusionOur data showed that ventilation dose-response can differ from perfusion dose-response for 20-30% of patients. Therefore, when performing thoracic dose-response in cancer patients, it is insufficient to look at ventilation or perfusion alone; but rather both modes of functional imaging may be needed when predicting for clinical outcomes.Advances in knowledgeThe significance of this study can be highlighted by the differences between the intrapatient dose-response assessments of this analysis compared to existing population-based dose-response analyses. Elucidating intrapatient ventilation and perfusion dose-response differences may be valuable in predicting pulmonary toxicity in lung cancer patients post-radiotherapy.

Project description:PurposeCurrently, several active clinical trials of functional lung avoidance radiation therapy using different imaging modalities for ventilation or perfusion are underway. Patients with lung cancer often show ventilation-perfusion mismatch, whereas the significance of dose-function metric remains unclear. The aim of the present study was to compare dose-ventilation metrics with dose-perfusion metrics for radiation therapy plan evaluation.Methods and materialsPretreatment 4-dimensional computed tomography and 99mTc-macroaggregated albumin single-photon emission computed tomography perfusion images of 60 patients with lung cancer treated with radiation therapy were analyzed. Ventilation images were created using the deformable image registration of 4-dimensional computed tomography image sets and image analysis for regional volume changes as a surrogate for ventilation. Ventilation and perfusion images were converted into percentile distribution images. Analyses included Pearson's correlation coefficient and comparison of agreements between the following dose-ventilation and dose-perfusion metrics: functional mean lung dose and functional percent lung function receiving 5, 10, 20, 30, and 40 Gy (fV5, fV10, fV20, fV30, and fV40, respectively).ResultsOverall, the dose-ventilation metrics were greater than the dose-perfusion metrics (ie, fV20, 26.3% ± 9.9% vs 23.9% ± 9.8%). Correlations between the dose-ventilation and dose-perfusion metrics were strong (range, r = 0.94-0.97), whereas the agreements widely varied among patients, with differences as large as 6.6 Gy for functional mean lung dose and 11.1% for fV20. Paired t test indicated that the dose-ventilation and dose-perfusion metrics were significantly different.ConclusionsStrong correlations were present between the dose-ventilation and dose-perfusion metrics. However, the agreement between the dose-ventilation and dose-perfusion metrics widely varied among patients, suggesting that ventilation-based radiation therapy plan evaluation may not be comparable to that based on perfusion. Future studies should elucidate the correlation of dose-function metrics with clinical pulmonary toxicity metrics.

Project description:ObjectiveCritical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation.MethodsTwo groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured.ResultsAirway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion.ConclusionsPressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.

Project description:BackgroundClinicians' interpretation of lung scan reports will determine which further management decisions are taken when potentially fatal pulmonary embolism (PE) is suspected.ObjectivesTo assess current referring clinicians' interpretation of the terminology used in ventilation/perfusion (V/Q) scan reports, whether this interpretation is affected by experience level, and how it affects clinical management decisions.MethodsThis was a questionnaire-based cross-sectional study. Between September 2020 and May 2021, 300 questionnaires were distributed among clinicians who refer patients for V/Q scans.ResultsOf the 162 clinicians who responded, 94% thought that there is >85% likelihood of PE or definitely PE present when a scan is reported as 'high probability of PE'; 87% interpreted 'low probability of PE' as <10% likelihood of PE or definitely no PE present. Overall, >70% of clinicians across all experience levels correctly interpreted the intended meaning of probability categories according to the Modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II criteria. Of the respondents, 77% agreed that clinically significant PE is ruled out by a normal scan. Further investigation for inconclusive findings, features of parenchymal lung disease and cardiomegaly were selected by 72%, 93% and 98% of clinicians, respectively.ConclusionThe findings of this study regarding high-probability scan results were in line with existing literature on lung scan report interpretation. However, our findings regarding low-probability scan results and negative V/Q scan specificity contrasted with the findings in these articles, suggesting that clinicians are now more familiar with lung scan interpretation guidelines. Experience level did not significantly affect interpretation of reports. Although most clinicians agreed that a negative scan excludes clinically significant PE, two-thirds of them would still subject the patient to further unnecessary investigations to exclude PE.Study synopsisWhat the study adds. Our findings regarding a low-probability ventilation/perfusion (V/Q) scan and the specificity of a negative V/Q scan contrasted with previous articles on lung scan interpretation, suggesting that clinicians are now more familiar with lung scan interpretation guidelines.Implications of the findings. Although most clinicians understood the negative predictive value of a V/Q scan, 20% would still investigate further with computed tomography pulmonary angiography or treat as confirmed pulmonary embolism. Education of clinicians about the negative predictive value of V/Q scans is important to avoid unnecessary radiation or anticoagulation.

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Characterizing spatial differences between SPECT-ventilation and SPECT-perfusion in patients with lung cancer undergoing radiotherapy.

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