A machine-learning regional clustering approach to understand ventilator-induced lung injury: a proof-of-concept experimental study.

BACKGROUND: The spatiotemporal progression and patterns of tissue deformation in ventilator-induced lung injury (VILI) remain understudied. Our aim was to identify lung clusters based on their regional mechanical behavior over space and time in lungs subjected to VILI using machine-learning techniques. RESULTS: Ten anesthetized pigs (27 ± 2 kg) were studied. Eight subjects were analyzed. End-inspiratory and end-expiratory lung computed tomography scans were performed at the beginning and after 12 h of one-hit VILI model. Regional image-based biomechanical analysis was used to determine end-expiratory aeration, tidal recruitment, and volumetric strain for both early and late stages. Clustering analysis was performed using principal component analysis and K-Means algorithms. We identified three different clusters of lung tissue: Stable, Recruitable Unstable, and Non-Recruitable Unstable. End-expiratory aeration, tidal recruitment, and volumetric strain were significantly different between clusters at early stage. At late stage, we found a step loss of end-expiratory aeration among clusters, lowest in Stable, followed by Unstable Recruitable, and highest in the Unstable Non-Recruitable cluster. Volumetric strain remaining unchanged in the Stable cluster, with slight increases in the Recruitable cluster, and strong reduction in the Unstable Non-Recruitable cluster. CONCLUSIONS: VILI is a regional and dynamic phenomenon. Using unbiased machine-learning techniques we can identify the coexistence of three functional lung tissue compartments with different spatiotemporal regional biomechanical behavior.

A strategy for estimating radiation dose to the blood in outpatient settings in differentiated thyroid cancer therapy with 131I-NaI.

BACKGROUND: Although standard operational procedures for pre-therapeutic dosimetry already exist for the determination of the maximum safe activity to treat differentiated thyroid cancer patients, empiric activity administration of 131I is still the most frequent way of treatment. In this way, the absorbed dose to the blood/bone marrow remains unknown. PURPOSE: In this work, we present a strategy to estimate radiation dose to the blood in an outpatient setting. METHODS: A mobile application was developed, which together with an off-the-shelf compact semiconductor radiation detector allows the determination of whole-body time-integrated activity coefficients. The methodology was tested in a cohort of 79 differentiated cancer patients who received therapeutic 131I activities. Post-therapeutic whole-body time-integrated activity coefficients were compared against pre-therapeutic estimates in a subset of 13 patients. RESULTS: The 95% limits of agreement between pre whole-body and post whole-body time integrated activity coefficients were [-14.4; 6.6] h when considering outliers and [-6.2; 3.6] h without outliers. A high dispersion in blood dose coefficients was found, with a four-fold difference between the highest and lower values. Blood doses were significantly higher for patients treated with dosimetrically guided activities than for empirical activities (median dose = 118 vs. 49 cGy, respectively). Blood dose coefficients were significantly lower for patients prepared with recombinant human thyroid stimulating hormone (rhTSH) than for patients prepared with thyroid hormone withdrawal. A low correlation between blood dose and administered activity was found in empirically treated patients (R2 = 0.26). CONCLUSIONS: We successfully implemented a post-therapeutic internal dosimetry methodology for differentiated thyroid cancer therapy with 131I, which allows to estimate dose to the blood from outpatient measurements with mobile devices. The proposed methodology avoids the need of daily visits to the nuclear medicine department, thus reducing the burden for the patient and for the staff.

Synthetic Attenuation Correction Maps for SPECT Imaging Using Deep Learning: A Study on Myocardial Perfusion Imaging.

(1) Background: The CT-based attenuation correction of SPECT images is essential for obtaining accurate quantitative images in cardiovascular imaging. However, there are still many SPECT cameras without associated CT scanners throughout the world, especially in developing countries. Performing additional CT scans implies troublesome planning logistics and larger radiation doses for patients, making it a suboptimal solution. Deep learning (DL) offers a revolutionary way to generate complementary images for individual patients at a large scale. Hence, we aimed to generate linear attenuation coefficient maps from SPECT emission images reconstructed without attenuation correction using deep learning. (2) Methods: A total of 384 SPECT myocardial perfusion studies that used 99mTc-sestamibi were included. A DL model based on a 2D U-Net architecture was trained using information from 312 patients. The quality of the generated synthetic attenuation correction maps (ACMs) and reconstructed emission values were evaluated using three metrics and compared to standard-of-care data using Bland-Altman plots. Finally, a quantitative evaluation of myocardial uptake was performed, followed by a semi-quantitative evaluation of myocardial perfusion. (3) Results: In a test set of 66 test patients, the ACM quality metrics were MSSIM = 0.97 ± 0.001 and NMAE = 3.08 ± 1.26 (%), and the reconstructed emission quality metrics were MSSIM = 0.99 ± 0.003 and NMAE = 0.23 ± 0.13 (%). The 95% limits of agreement (LoAs) at the voxel level for reconstructed SPECT images were: [-9.04; 9.00]%, and for the segment level, they were [-11; 10]%. The 95% LoAs for the Summed Stress Score values between the images reconstructed were [-2.8, 3.0]. When global perfusion scores were assessed, only 2 out of 66 patients showed changes in perfusion categories. (4) Conclusion: Deep learning can generate accurate attenuation correction maps from non-attenuation-corrected cardiac SPECT images. These high-quality attenuation maps are suitable for attenuation correction in myocardial perfusion SPECT imaging and could obviate the need for additional imaging in standalone SPECT scanners.

Improved PET quantification and harmonization by adaptive denoising.

PURPOSE: Quantification in positron emission tomography (PET) is subject to bias due to physical and technical limitations. The goal of quantitative harmonization is to achieve comparable measurements between different scanners, thus enabling multicenter clinical trials. Clinical guidelines, such as those from the European Association of Nuclear Medicine (EANM), recommend harmonizing PET reconstructions to bring contrast recovery coefficients (CRCs) within specifications. However, these harmonized reconstructions can show quantitative biases. In this work we improve harmonization by using a novel adaptive filtering scheme. Our goal was to obtain low quantification bias and high peak signal to noise ratio (PSNR) values at the same time. METHODS: a novel three-stage adaptive denoising filter was implemented. Filter parameters were optimized to achieve both high PSNR in a digital brain phantom and low quantitative bias of maximum CRC values (CRCmax) obtained from a National Electrical Manufacturers Association (NEMA) PET image quality phantom. The NEMA phantom was scanned on several PET/CT scanners and reconstructed without postfilters. The optimal filter settings found for a training dataset were then applied to testing reconstructions from other scanners. Harmonization limits were defined using the 95% confidence intervals across reconstructions. RESULTS: Average CRCmax values close to unity (± 5%) were achieved for spheres with diameter equal or greater than 13 mm for the training dataset. PSNR values were comparable to other state-of-the-art filter results. Using the same optimal filter settings for the testing datasets, similar quantitative results were found. Lesion conspicuity was improved on clinical scans when compared with EANM reconstructions, with no visible artifacts. CONCLUSIONS: Our three-stage adaptive filter achieved state-of-the-art quantitative performance for PET imaging. Harmonization tolerances with lower bias and variance than EANM guidelines were achieved for a variety of scanner models. CRCmax values were close to unity and the quantification variability was reduced when compared with standard reconstructions.

Protocols for Harmonized Quantification and Noise Reduction in Low-Dose Oncologic 18F-FDG PET/CT Imaging.

Oncologic 18F-FDG PET/CT acquisition and reconstruction protocols need to be optimized for both quantitative and detection tasks. To date, most studies have focused on either quantification or noise, leading to quantitative harmonization guidelines or appropriate noise levels. We developed and evaluated protocols that provide harmonized quantitation with optimal amounts of noise as a function of acquisition parameters and body mass. Methods: Multiple image acquisitions (n = 17) of the International Electrotechnical Commission/National Electrical Manufacturers Association PET image-quality phantom were performed with variable counting statistics. Phantom images were reconstructed with 3-dimensional ordered-subset expectation maximization (OSEM3D) and point-spread function (PSF) for harmonized quantification of the contrast recovery coefficient of the maximum pixel value (CRC max ). The lowest counting statistics that resulted in compliance with European Association of Nuclear Medicine recommendations for CRC max and CRC max variability were used as optimization metrics. Image noise in the liver of 48 typical oncologic 18F-FDG PET/CT studies was analyzed with OSEM3D and PSF harmonized reconstructions. We also evaluated 164 additional 18F-FDG PET/CT reconstructed list-mode images to derive analytic expressions that predict image quality and noise variability. Phantom-to-subject translational analysis was used to derive optimized acquisition and reconstruction protocols. Results: For harmonized quantitation levels, PSF reconstructions yielded decreased noise and lower CRC max variability than regular OSEM3D reconstructions, suggesting they could enable a decreased activity regimen for matched performance. Conclusion: PSF reconstruction with a 7-mm postprocessing filter can provide harmonized quantification performance and acceptable image noise levels with injected activity, duration, and mass settings using a 260 MBq⋅s/kg acquisition parameter at scan time. Similarly, OSEM3D with a 5-mm postprocessing filter can provide similar performance with 401 MBq⋅s/kg.

Optimization of oncological ¹8F-FDG PET/CT imaging based on a multiparameter analysis.

PURPOSE: This paper describes a method to achieve consistent clinical image quality in (18)F-FDG scans accounting for patient habitus, dose regimen, image acquisition, and processing techniques. METHODS: Oncological PET/CT scan data for 58 subjects were evaluated retrospectively to derive analytical curves that predict image quality. Patient noise equivalent count rate and coefficient of variation (CV) were used as metrics in their analysis. Optimized acquisition protocols were identified and prospectively applied to 179 subjects. RESULTS: The adoption of different schemes for three body mass ranges (<60 kg, 60-90 kg, >90 kg) allows improved image quality with both point spread function and ordered-subsets expectation maximization-3D reconstruction methods. The application of this methodology showed that CV improved significantly (p < 0.0001) in clinical practice. CONCLUSIONS: Consistent oncological PET/CT image quality on a high-performance scanner was achieved from an analysis of the relations existing between dose regimen, patient habitus, acquisition, and processing techniques. The proposed methodology may be used by PET/CT centers to develop protocols to standardize PET/CT imaging procedures and achieve better patient management and cost-effective operations.

Relación entre los patrones de viabilidad, flujo miocárdico y la anatomía coronaria mediante tomografía por emisión de positrones integrada con tomografía multicorte / Relationship between Myocardial Viability, Myocardial Flow and Coronary Anatomy by Positron Emission Tomography Integrated with Multislice Computed Tomography

Introducción La relación entre la viabilidad, el flujo miocárdico y el grado de estenosis epicárdica en pacientes con enfermedad coronaria y disfunción ventricular izquierda está poco investigada. Objetivo Determinar si los patrones de viabilidad por tomografía por emisión de positrones (PET) y el flujo miocárdico en reposo se relacionan con el grado de estenosis epicárdica. Material y métodos Se evaluó la viabilidad en 27 pacientes mediante el análisis combinado de la perfusión con 13N-amonio (13NH3) y el metabolismo con 18F-fluoro-2-desoxiglucosa (FDG) para identificar cuatro patrones PET: match (hipocaptación concordante de ambos radiotrazadores), mismatch (hipoperfusión con captación preservada de FDG), mismatch inverso (perfusión preservada e hipocaptación de FDG) y perfusión/metabolismo conservados. El flujo absoluto se calculó mediante un modelo bicompartimental. Las estenosis se clasificaron en leves ( 50%), graves (> 70%) y críticas (= 90%). Resultados De 459 segmentos resultaron match el 33%, mismatch el 12%, mismatch inverso el 11% y conservado el 44%. El flujo para mismatch, mismatch inverso y conservado fue mayor que para los segmentos con match (p < 0,01). Quince lesiones fueron leves, 7 moderadas, 20 graves y 39 críticas. No hubo correlación entre el grado de estenosis y los patrones de viabilidad (R < 0,2; p = ns) ni con los valores de flujo (R = 0,12). El análisis por territorio vascular no mostró correlación con el grado de estenosis (p = ns). Conclusiones No hubo correlación entre los patrones PET, el grado de estenosis epicárdica y el flujo mio-cárdico, lo que sugiere que la anatomía coronaria no puede discriminar miocardio viable del necrótico ni predecir el estado del flujo miocárdico en pacientes con disfunción ventricular izquierda.(AU)

Background The relationship between myocardial viability, myocardial flow and the degree of epicardial coronary stenosis in patients with coronary artery disease and left ventricular dysfunction is unclear. Objective The purpose of this study is to determine whether positron emission tomography (PET) viability and myocardial flow at rest correlate with the degree of epicardial coronary stenosis. Methods Myocardial viability was evaluated in 27 patients by the combined analysis of 13N-Ammonia (13NH3) perfusion and 18F-fluoro-2-deoxyglucose (FDG) metabolism to identify four PET patterns: match (concordant reduced uptake of both radiotracers), mismatch (hypoperfusion with preserved FDG uptake), reverse mismatch (preserved perfusion and reduced FDG uptake) and preserved uptake of both radiotracers. Myocardial blood flow was calculated using a two-compartment model. Coronary artery stenosis was classified as mild (50%), severe (>70%) and critical (= 90%). Results From 459 analyzed segments, 33% were match, 12% mismatch, 11% reverse-mismatch and 44% preserved. Mismatch, reverse-mismatch and preserved patterns exhibited higher flows than the match pattern (p < 0.01). Fifteen coronary lesions were mild, 7 moderate, 20 severe and 39 critical. There was no correlation between the degree of coronary stenosis and viability patterns (R< 0.2, p=NS) or blood flow values (R=0.12). Analysis by vascular territory did not correlate with the degree of coronary stenosis (p=NS). Conclusions Lack of correlation between PET viability patterns, degree of epicardial stenosis and myocardial blood flow suggest that coronary anatomy can neither differentiate viable from necrotic myocardium nor predict the functional status of myocardial flow in patients with left ventricular dysfunction.(AU)

Relación entre los patrones de viabilidad, flujo miocárdico y la anatomía coronaria mediante tomografía por emisión de positrones integrada con tomografía multicorte / Relationship between Myocardial Viability, Myocardial Flow and Coronary Anatomy by Positron Emission Tomography Integrated with Multislice Computed Tomography

Introducción La relación entre la viabilidad, el flujo miocárdico y el grado de estenosis epicárdica en pacientes con enfermedad coronaria y disfunción ventricular izquierda está poco investigada. Objetivo Determinar si los patrones de viabilidad por tomografía por emisión de positrones (PET) y el flujo miocárdico en reposo se relacionan con el grado de estenosis epicárdica. Material y métodos Se evaluó la viabilidad en 27 pacientes mediante el análisis combinado de la perfusión con 13N-amonio (13NH3) y el metabolismo con 18F-fluoro-2-desoxiglucosa (FDG) para identificar cuatro patrones PET: match (hipocaptación concordante de ambos radiotrazadores), mismatch (hipoperfusión con captación preservada de FDG), mismatch inverso (perfusión preservada e hipocaptación de FDG) y perfusión/metabolismo conservados. El flujo absoluto se calculó mediante un modelo bicompartimental. Las estenosis se clasificaron en leves ( 50%), graves (> 70%) y críticas (= 90%). Resultados De 459 segmentos resultaron match el 33%, mismatch el 12%, mismatch inverso el 11% y conservado el 44%. El flujo para mismatch, mismatch inverso y conservado fue mayor que para los segmentos con match (p < 0,01). Quince lesiones fueron leves, 7 moderadas, 20 graves y 39 críticas. No hubo correlación entre el grado de estenosis y los patrones de viabilidad (R < 0,2; p = ns) ni con los valores de flujo (R = 0,12). El análisis por territorio vascular no mostró correlación con el grado de estenosis (p = ns). Conclusiones No hubo correlación entre los patrones PET, el grado de estenosis epicárdica y el flujo mio-cárdico, lo que sugiere que la anatomía coronaria no puede discriminar miocardio viable del necrótico ni predecir el estado del flujo miocárdico en pacientes con disfunción ventricular izquierda.

Background The relationship between myocardial viability, myocardial flow and the degree of epicardial coronary stenosis in patients with coronary artery disease and left ventricular dysfunction is unclear. Objective The purpose of this study is to determine whether positron emission tomography (PET) viability and myocardial flow at rest correlate with the degree of epicardial coronary stenosis. Methods Myocardial viability was evaluated in 27 patients by the combined analysis of 13N-Ammonia (13NH3) perfusion and 18F-fluoro-2-deoxyglucose (FDG) metabolism to identify four PET patterns: match (concordant reduced uptake of both radiotracers), mismatch (hypoperfusion with preserved FDG uptake), reverse mismatch (preserved perfusion and reduced FDG uptake) and preserved uptake of both radiotracers. Myocardial blood flow was calculated using a two-compartment model. Coronary artery stenosis was classified as mild (50%), severe (>70%) and critical (= 90%). Results From 459 analyzed segments, 33% were match, 12% mismatch, 11% reverse-mismatch and 44% preserved. Mismatch, reverse-mismatch and preserved patterns exhibited higher flows than the match pattern (p < 0.01). Fifteen coronary lesions were mild, 7 moderate, 20 severe and 39 critical. There was no correlation between the degree of coronary stenosis and viability patterns (R< 0.2, p=NS) or blood flow values (R=0.12). Analysis by vascular territory did not correlate with the degree of coronary stenosis (p=NS). Conclusions Lack of correlation between PET viability patterns, degree of epicardial stenosis and myocardial blood flow suggest that coronary anatomy can neither differentiate viable from necrotic myocardium nor predict the functional status of myocardial flow in patients with left ventricular dysfunction.