Review of Hyperpolarized Pulmonary Functional 129 Xe MR for Long-COVID.

The respiratory consequences of acute COVID-19 infection and related symptoms tend to resolve 4 weeks post-infection. However, for some patients, new, recurrent, or persisting symptoms remain beyond the acute phase and persist for months, post-infection. The symptoms that remain have been referred to as long-COVID. A number of research sites employed 129 Xe magnetic resonance imaging (MRI) during the pandemic and evaluated patients post-infection, months after hospitalization or home-based care as a way to better understand the consequences of infection on 129 Xe MR gas-exchange and ventilation imaging. A systematic review and comprehensive search were employed using MEDLINE via PubMed (April 2023) using the National Library of Medicine's Medical Subject Headings and key words: post-COVID-19, MRI, 129 Xe, long-COVID, COVID pneumonia, and post-acute COVID-19 syndrome. Fifteen peer-reviewed manuscripts were identified including four editorials, a single letter to the editor, one review article, and nine original research manuscripts (2020-2023). MRI and MR spectroscopy results are summarized from these prospective, controlled studies, which involved small sample sizes ranging from 9 to 76 participants. Key findings included: 1) 129 Xe MRI gas-exchange and ventilation abnormalities, 3 months post-COVID-19 infection, and 2) a combination of MRI gas-exchange and ventilation abnormalities alongside persistent symptoms in patients hospitalized and not hospitalized for COVID-19, 1-year post-infection. The persistence of respiratory symptoms and 129 Xe MRI abnormalities in the context of normal or nearly normal pulmonary function test results and chest computed tomography (CT) was consistent. Longitudinal improvements were observed in long-term follow-up of long-COVID patients but mean 129 Xe gas-exchange, ventilation heterogeneity values and symptoms remained abnormal, 1-year post-infection. Pulmonary functional MRI using inhaled hyperpolarized 129 Xe gas has played a role in detecting gas-exchange and ventilation abnormalities providing complementary information that may help develop our understanding of the root causes of long-COVID. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

Residual Lung Abnormalities after COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID-19 Study.

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP-COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83-155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05-1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00-1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07-1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6-9.5), rising to 11.7% (95% CrI, 10.3-13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19-related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.

Gas exchange and ventilation imaging of healthy and COPD subjects using hyperpolarized xenon-129 MRI and a 3D alveolar gas-exchange model.

OBJECTIVES: To investigate the utility of hyperpolarized xenon-129 (HPX) gas-exchange magnetic resonance imaging (MRI) and modeling in a chronic obstructive pulmonary disease (COPD) cohort in comparison to a minimal CT-diagnosed emphysema (MCTE) cohort and a healthy cohort. METHODS: A total of 25 subjects were involved in this study including COPD (n = 8), MCTE (n = 3), and healthy (n = 14) subjects. The COPD subjects were scanned using HPX ventilation, gas-exchange MRI, and volumetric CT. The healthy subjects were scanned using the same HPX gas-exchange MRI protocol with 9 of them scanned twice, 3 weeks apart. The coefficient of variation (CV) was used to quantify image heterogeneities. A three-dimensional computational fluid dynamic (CFD) model of gas exchange was used to derive functional volumes of pulmonary tissue, capillaries, and veins. RESULTS: The CVs of gas distributions in the images showed that there was a statistically significant difference between the COPD and healthy subjects (p < 0.0001). The functional volumes of pulmonary tissue, capillaries, and veins were significantly lower in the subjects with COPD than in the healthy subjects (p < 0.001). The functional volume of pulmonary tissue was found to be (i) statistically different between the healthy and MCTE groups (p = 0.02) and (ii) dependent on the age of the subjects in the healthy group (p = 0.0008) while their CVs (p = 0.13) were not. CONCLUSION: The novel HPX gas-exchange MRI and CFD model distinguished the healthy cohort from the MCTE and COPD cohorts. The proposed technique also showed that the functional volume of pulmonary tissue decreases with aging in the healthy group. KEY POINTS: • The ventilation and gas-exchange imaging with hyperpolarized xenon-129 MRI has enabled the identification of gas-exchange variation between COPD and healthy groups. • This novel technique was promising to be sensitive to minimal CT-diagnosed emphysema and age-related changes in gas-exchange parameter in a small pilot cohort.

Artificial Intelligence Tool for Assessment of Indeterminate Pulmonary Nodules Detected with CT.

Background Limited data are available regarding whether computer-aided diagnosis (CAD) improves assessment of malignancy risk in indeterminate pulmonary nodules (IPNs). Purpose To evaluate the effect of an artificial intelligence-based CAD tool on clinician IPN diagnostic performance and agreement for both malignancy risk categories and management recommendations. Materials and Methods This was a retrospective multireader multicase study performed in June and July 2020 on chest CT studies of IPNs. Readers used only CT imaging data and provided an estimate of malignancy risk and a management recommendation for each case without and with CAD. The effect of CAD on average reader diagnostic performance was assessed using the Obuchowski-Rockette and Dorfman-Berbaum-Metz method to calculate estimates of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Multirater Fleiss κ statistics were used to measure interobserver agreement for malignancy risk and management recommendations. Results A total of 300 chest CT scans of IPNs with maximal diameters of 5-30 mm (50.0% malignant) were reviewed by 12 readers (six radiologists, six pulmonologists) (patient median age, 65 years; IQR, 59-71 years; 164 [55%] men). Readers' average AUC improved from 0.82 to 0.89 with CAD (P < .001). At malignancy risk thresholds of 5% and 65%, use of CAD improved average sensitivity from 94.1% to 97.9% (P = .01) and from 52.6% to 63.1% (P < .001), respectively. Average reader specificity improved from 37.4% to 42.3% (P = .03) and from 87.3% to 89.9% (P = .05), respectively. Reader interobserver agreement improved with CAD for both the less than 5% (Fleiss κ, 0.50 vs 0.71; P < .001) and more than 65% (Fleiss κ, 0.54 vs 0.71; P < .001) malignancy risk categories. Overall reader interobserver agreement for management recommendation categories (no action, CT surveillance, diagnostic procedure) also improved with CAD (Fleiss κ, 0.44 vs 0.52; P = .001). Conclusion Use of computer-aided diagnosis improved estimation of indeterminate pulmonary nodule malignancy risk on chest CT scans and improved interobserver agreement for both risk stratification and management recommendations. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Yanagawa in this issue.

Developing an understanding of artificial intelligence lung nodule risk prediction using insights from the Brock model.

OBJECTIVES: To determine if predictions of the Lung Cancer Prediction convolutional neural network (LCP-CNN) artificial intelligence (AI) model are analogous to the Brock model. METHODS: In total, 10,485 lung nodules in 4660 participants from the National Lung Screening Trial (NLST) were analysed. Both manual and automated nodule measurements were inputted into the Brock model, and this was compared to LCP-CNN. The performance of an experimental AI model was tested after ablating imaging features in a manner analogous to removing predictors from the Brock model. First, the nodule was ablated leaving lung parenchyma only. Second, a sphere of the same size as the nodule was implanted in the parenchyma. Third, internal texture of both nodule and parenchyma was ablated. RESULTS: Automated axial diameter (AUC 0.883) and automated equivalent spherical diameter (AUC 0.896) significantly improved the accuracy of Brock when compared to manual measurement (AUC 0.873), although not to the level of the LCP-CNN (AUC 0.936). Ablating nodule and parenchyma texture (AUC 0.915) led to a small drop in AI predictive accuracy, as did implanting a sphere of the same size as the nodule (AUC 0.889). Ablating the nodule leaving parenchyma only led to a large drop in AI performance (AUC 0.717). CONCLUSIONS: Feature ablation is a feasible technique for understanding AI model predictions. Nodule size and morphology play the largest role in AI prediction, with nodule internal texture and background parenchyma playing a limited role. This is broadly analogous to the relative importance of morphological factors over clinical factors within the Brock model. KEY POINTS: • Brock lung cancer risk prediction accuracy was significantly improved using automated axial or equivalent spherical measurements of lung nodule diameter, when compared to manual measurements. • Predictive accuracy was further improved by using the Lung Cancer Prediction convolutional neural network, an artificial intelligence-based model which obviates the requirement for nodule measurement. • Nodule size and morphology are important factors in artificial intelligence lung cancer risk prediction, with nodule texture and background parenchyma contributing a small, but measurable, role.

Lobar Ventilation in Patients with COPD Assessed with the Full-Scale Airway Network Flow Model and Xenon-enhanced Dual-Energy CT.

Background The full-scale airway network (FAN) flow model shows excellent agreement with limited functional imaging data but requires further validation prior to clinical use. Purpose To validate the ventilation distributions computed with the FAN flow model with xenon ventilation from xenon-enhanced dual-energy (DE) CT in participants with chronic obstructive pulmonary disease (COPD). Materials and Methods In this prospective study, the FAN model extracted structural data from xenon-enhanced DE CT images of men with COPD scanned between June 2012 and July 2013 to compute gas ventilation dynamics. The ventilation distributions on the middle cross-section plane, percentage lobar ventilation, and ventilation heterogeneity quantified by the coefficient of variation (CV) were compared between xenon-enhanced DE CT imaging and the FAN model. The relationship between the ventilation parameters with the densitometry and pulmonary function test results was demonstrated. The agreements and correlations between the parameters were measured using the concordance correlation coefficient and the Pearson correlation coefficient. Results Twenty-two men with COPD (mean age, 67 years ± 7 [standard deviation]) were evaluated. The percentage lobar ventilation computed with FAN showed a strong positive correlation with xenon-enhanced DE CT data (r = 0.7, P < .001). Ninety-five percent of lobar ventilation CV differences lay within 95% confidence intervals. Correlations of the percentage lobar ventilation were negative for percentage emphysema (xenon-enhanced DE CT: r = -0.38, P < .001; FAN: r = -0.23, P = .02) but were positive for percentage normal tissue volume (xenon-enhanced DE CT: r = 0.78, P < .001; FAN: r = 0.45, P < .001). Lung CVs of FAN revealed negative correlations with the spirometry results (CVFAN vs percentage predicted forced expiratory volume in 1 second: r = -0.75, P < .001; CVFAN vs ratio of forced expiratory volume in 1 second to forced vital capacity: r = -0.67, P < .001). Conclusion The full-scale airway network modeled lobar ventilation in patients with chronic obstructive pulmonary disease correlated with the xenon-enhanced dual-energy CT imaging data. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Parraga and Eddy in this issue.

Radiomics in predicting treatment response in non-small-cell lung cancer: current status, challenges and future perspectives.

OBJECTIVES: Radiomics is the extraction of quantitative data from medical imaging, which has the potential to characterise tumour phenotype. The radiomics approach has the capacity to construct predictive models for treatment response, essential for the pursuit of personalised medicine. In this literature review, we summarise the current status and evaluate the scientific and reporting quality of radiomics research in the prediction of treatment response in non-small-cell lung cancer (NSCLC). METHODS: A comprehensive literature search was conducted using the PubMed database. A total of 178 articles were screened for eligibility and 14 peer-reviewed articles were included. The radiomics quality score (RQS), a radiomics-specific quality metric emulating the TRIPOD guidelines, was used to assess scientific and reporting quality. RESULTS: Included studies reported several predictive markers including first-, second- and high-order features, such as kurtosis, grey-level uniformity and wavelet HLL mean respectively, as well as PET-based metabolic parameters. Quality assessment demonstrated a low median score of + 2.5 (range - 5 to + 9), mainly reflecting a lack of reproducibility and clinical evaluation. There was extensive heterogeneity between studies due to differences in patient population, cancer stage, treatment modality, follow-up timescales and radiomics workflow methodology. CONCLUSIONS: Radiomics research has not yet been translated into clinical use. Efforts towards standardisation and collaboration are needed to identify reproducible radiomic predictors of response. Promising radiomic models must be externally validated and their impact evaluated within the clinical pathway before they can be implemented as a clinical decision-making tool to facilitate personalised treatment for patients with NSCLC. KEY POINTS: • The included studies reported several promising radiomic markers of treatment response in lung cancer; however, there was a lack of reproducibility between studies. • Quality assessment using the radiomics quality score (RQS) demonstrated a low median total score of + 2.5 (range - 5 to + 9). • Future radiomics research should focus on implementation of standardised radiomics features and software, together with external validation in a prospective setting.

External validation of a convolutional neural network artificial intelligence tool to predict malignancy in pulmonary nodules.

BACKGROUND: Estimation of the risk of malignancy in pulmonary nodules detected by CT is central in clinical management. The use of artificial intelligence (AI) offers an opportunity to improve risk prediction. Here we compare the performance of an AI algorithm, the lung cancer prediction convolutional neural network (LCP-CNN), with that of the Brock University model, recommended in UK guidelines. METHODS: A dataset of incidentally detected pulmonary nodules measuring 5-15 mm was collected retrospectively from three UK hospitals for use in a validation study. Ground truth diagnosis for each nodule was based on histology (required for any cancer), resolution, stability or (for pulmonary lymph nodes only) expert opinion. There were 1397 nodules in 1187 patients, of which 234 nodules in 229 (19.3%) patients were cancer. Model discrimination and performance statistics at predefined score thresholds were compared between the Brock model and the LCP-CNN. RESULTS: The area under the curve for LCP-CNN was 89.6% (95% CI 87.6 to 91.5), compared with 86.8% (95% CI 84.3 to 89.1) for the Brock model (p≤0.005). Using the LCP-CNN, we found that 24.5% of nodules scored below the lowest cancer nodule score, compared with 10.9% using the Brock score. Using the predefined thresholds, we found that the LCP-CNN gave one false negative (0.4% of cancers), whereas the Brock model gave six (2.5%), while specificity statistics were similar between the two models. CONCLUSION: The LCP-CNN score has better discrimination and allows a larger proportion of benign nodules to be identified without missing cancers than the Brock model. This has the potential to substantially reduce the proportion of surveillance CT scans required and thus save significant resources.

Intercostal vessel screening prior to pleural interventions by the respiratory physician: a prospective study of real world practice.

INTRODUCTION: The rising incidence of pleural disease is seeing an international growth of pleural services, with physicians performing an ever-increasing volume of pleural interventions. These are frequently conducted at sites without immediate access to thoracic surgery or interventional radiology and serious complications such as pleural bleeding are likely to be under-reported. AIM: To assess whether intercostal vessel screening can be performed by respiratory physicians at the time of pleural intervention, as an additional step that could potentially enhance safe practice. METHODS: This was a prospective, observational study of 596 ultrasound-guided pleural procedures conducted by respiratory physicians and trainees in a tertiary centre. Operators did not have additional formal radiology training. Intercostal vessel screening was performed using a low frequency probe and the colour Doppler feature. RESULTS: The intercostal vessels were screened in 95% of procedures and the intercostal artery (ICA) was successfully identified in 53% of cases. Screening resulted in an overall site alteration rate of 16% in all procedures, which increased to 30% when the ICA was successfully identified. This resulted in procedure abandonment in 2% of cases due to absence of a suitable entry site. Intercostal vessel screening was shown to be of particular value in the context of image-guided pleural biopsy. CONCLUSION: Intercostal vessel screening is a simple and potentially important additional step that can be performed by respiratory physicians at the time of pleural intervention without advanced ultrasound expertise. Whether the widespread use of this technique can improve safety requires further evaluation in a multi-centre setting with a robust prospective study.

CT-based Airway Flow Model to Assess Ventilation in Chronic Obstructive Pulmonary Disease: A Pilot Study.

Background The lack of functional information in thoracic CT remains a limitation of its use in the clinical management of chronic obstructive pulmonary disease (COPD). Purpose To compare the distribution of pulmonary ventilation assessed by a CT-based full-scale airway network (FAN) flow model with hyperpolarized xenon 129 (129Xe) MRI (hereafter, 129Xe MRI) and technetium 99m-diethylenetriaminepentaacetic acid aerosol SPECT ventilation imaging (hereafter, V-SPECT) in participants with COPD. Materials and Methods In this prospective study performed between May and August 2017, pulmonary ventilation in participants with COPD was computed by using the FAN flow model. The modeled pulmonary ventilation was compared with functional imaging data from breath-hold time-series 129Xe MRI and V-SPECT. FAN-derived ventilation images on the coronal plane and volumes of interest were compared with functional lung images. Percentage lobar ventilation estimated by the FAN model was compared with that measured at 129Xe MRI and V-SPECT. The statistical significance of ventilation distribution between FAN and functional images was demonstrated with the Spearman correlation coefficient and χ2 distance. Results For this study, nine participants (seven men [mean age, 65 years ± 5 {standard deviation}] and two women [mean age, 63 years ± 7]) with COPD that was Global Initiative for Chronic Obstructive Lung Disease stage II-IV were enrolled. FAN-modeled ventilation profile showed strong positive correlation with images from 129Xe MRI (ρ = 0.67; P < .001) and V-SPECT (ρ = 0.65; P < .001). The χ2 distances of the ventilation histograms in the volumes of interest between the FAN and 129Xe MRI and FAN and V-SPECT were 0.16 ± 0.08 and 0.28 ± 0.14, respectively. The ratios of lobar ventilations in the models were linearly correlated to images from 129Xe MRI (ρ = 0.67; P < .001) and V-SPECT (ρ = 0.59; P < .001). Conclusion A CT-based full-scale airway network flow model provided regional pulmonary ventilation information for chronic obstructive pulmonary disease and correlates with hyperpolarized xenon 129 MRI and technetium 99m-diethylenetriaminepentaacetic acid aerosol SPECT ventilation imaging. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Schiebler and Parraga in this issue.

Focused Ultrasound Hyperthermia for Targeted Drug Release from Thermosensitive Liposomes: Results from a Phase I Trial.

Purpose To demonstrate the feasibility and safety of using focused ultrasound planning models to determine the treatment parameters needed to deliver volumetric mild hyperthermia for targeted drug delivery without real-time thermometry. Materials and Methods This study was part of the Targeted Doxorubicin, or TARDOX, phase I prospective trial of focused ultrasound-mediated, hyperthermia-triggered drug delivery to solid liver tumors ( ClinicalTrials.gov identifier NCT02181075). Ten participants (age range, 49-68 years; average age, 60 years; four women) were treated from March 2015 to March 2017 by using a clinically approved focused ultrasound system to release doxorubicin from lyso-thermosensitive liposomes. Ultrasonic heating of target tumors (treated volume: 11-73 cm3 [mean ± standard deviation, 50 cm3 ± 26]) was monitored in six participants by using a minimally invasive temperature sensor; four participants were treated without real-time thermometry. For all participants, CT images were used with a patient-specific hyperthermia model to define focused ultrasound treatment plans. Feasibility was assessed by comparing model-prescribed focused ultrasound powers to those implemented for treatment. Safety was assessed by evaluating MR images and biopsy specimens for evidence of thermal ablation and monitoring adverse events. Results The mean difference between predicted and implemented treatment powers was -0.1 W ± 17.7 (n = 10). No evidence of focused ultrasound-related adverse effects, including thermal ablation, was found. Conclusion In this 10-participant study, the authors confirmed the feasibility of using focused ultrasound-mediated hyperthermia planning models to define treatment parameters that safely enabled targeted, noninvasive drug delivery to liver tumors while monitored with B-mode guidance and without real-time thermometry. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Dickey and Levi-Polyachenko in this issue.

Comparison of Prostate Biopsy with or without Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Detection: An Observational Cohort Study.

PURPOSE: We hypothesized that 1) introducing prebiopsy multiparametric magnetic resonance imaging would increase the diagnostic yield of transrectal prostate biopsy and 2) this would inform recommendations regarding systematic transrectal prostate biopsy in the setting of negative prebiopsy multiparametric magnetic resonance imaging. MATERIALS AND METHODS: A total of 997 biopsy naïve patients underwent transrectal prostate biopsy alone to June 2016 (cohort 1) and thereafter 792 underwent transrectal prostate biopsy following prebiopsy multiparametric magnetic resonance imaging (cohort 2). Patients with lesions on prebiopsy multiparametric magnetic resonance imaging underwent cognitive targeted plus systematic transrectal prostate biopsy. Patients without lesions underwent systematic transrectal prostate biopsy. RESULTS: Cohort 2 comprised younger men (age 68 vs 69 years, p = 0.01) with lower prostate specific antigen (7.6 vs 7.9 ng/ml, p = 0.024) and smaller prostate volume (56.1 vs 62 cc, p = 0.006). In cohort 2 vs cohort 1 there was no increase in overall prostate cancer detection (57.6% vs 56.7%, p = 0.701), the Gleason Grade Group or the number of positive cores (each p >0.05). Increased multifocal prostatic intraepithelial neoplasia, maximum prostate cancer core length (5 mm or greater vs less than 5 mm) and radical surgery/high intensity focused ultrasound (each p <0.05) were observed in cohort 2. For Gleason Grade Group 2-5 prostate cancer negative prebiopsy multiparametric magnetic resonance imaging had 88.1% sensitivity, 59.8% specificity, 67.8% positive predictive value and 84% negative predictive value. For negative prebiopsy multiparametric magnetic resonance images a prostate specific antigen density cutoff of 0.15 ng/ml2 or greater increased clinically significant prostate cancer detection only if the latter was defined as Gleason Grade Group 3-5 disease and/or tumor length 6 mm or greater. CONCLUSIONS: Introducing prebiopsy multiparametric magnetic resonance imaging in our clinical setting increased the diagnostic yield of prostate cancer per biopsy core. Not performing a systematic transrectal prostate biopsy when prebiopsy multiparametric magnetic resonance imaging was negative would have led to under detection of 15.1% of Gleason Grade Group 2 or greater prostate cancer cases (approximately 1 in 6).

Magnetic resonance imaging of the time course of hyperpolarized 129Xe gas exchange in the human lungs and heart.

PURPOSE: To perform magnetic resonance imaging (MRI), human lung imaging, and quantification of the gas-transfer dynamics of hyperpolarized xenon-129 (HPX) from the alveoli into the blood plasma. MATERIALS AND METHODS: HPX MRI with iterative decomposition of water and fat with echo asymmetry and least-square estimation (IDEAL) approach were used with multi-interleaved spiral k-space sampling to obtain HPX gas and dissolved phase images. IDEAL time-series images were then obtained from ten subjects including six normal subjects and four patients with pulmonary emphysema to test the feasibility of the proposed technique for capturing xenon-129 gas-transfer dynamics (XGTD). The dynamics of xenon gas diffusion over the entire lung was also investigated by measuring the signal intensity variations between three regions of interest, including the left and right lungs and the heart using Welch's t test. RESULTS: The technique enabled the acquisition of HPX gas and dissolved phase compartment images in a single breath-hold interval of 8 s. The y-intersect of the XGTD curves were also found to be statistically lower in the patients with lung emphysema than in the healthy group (p < 0.05). CONCLUSION: This time-series IDEAL technique enables the visualization and quantification of inhaled xenon from the alveoli to the left ventricle with a clinical gradient strength magnet during a single breath-hold, in healthy and diseased lungs. KEY POINTS: • The proposed hyperpolarized xenon-129 gas and dissolved magnetic resonance imaging technique can provide regional and temporal measurements of xenon-129 gas-transfer dynamics. • Quantitative measurement of xenon-129 gas-transfer dynamics from the alveolar to the heart was demonstrated in normal subjects and pulmonary emphysema. • Comparison of gas-transfer dynamics in normal subjects and pulmonary emphysema showed that the proposed technique appears sensitive to changes affecting the alveoli, pulmonary interstitium, and capillaries.

Time-series hyperpolarized xenon-129 MRI of lobar lung ventilation of COPD in comparison to V/Q-SPECT/CT and CT.

PURPOSE: To derive lobar ventilation in patients with chronic obstructive pulmonary disease (COPD) using a rapid time-series hyperpolarized xenon-129 (HPX) magnetic resonance imaging (MRI) technique and compare this to ventilation/perfusion single-photon emission computed tomography (V/Q-SPECT), correlating the results with high-resolution computed tomography (CT) and pulmonary function tests (PFTs). MATERIALS AND METHODS: Twelve COPD subjects (GOLD stages I-IV) participated in this study and underwent HPX-MRI, V/Q-SPECT/CT, high-resolution CT, and PFTs. HPX-MRI was performed using a novel time-series spiral k-space sampling approach. Relative percentage ventilations were calculated for individual lobe for comparison to the relative SPECT lobar ventilation and perfusion. The absolute HPX-MRI percentage ventilation in each lobe was compared to the absolute CT percentage emphysema score calculated using a signal threshold method. Pearson's correlation and linear regression tests were performed to compare each imaging modality. RESULTS: Strong correlations were found between the relative lobar percentage ventilation with HPX-MRI and percentage ventilation SPECT (r = 0.644; p < 0.001) and percentage perfusion SPECT (r = 0.767; p < 0.001). The absolute CT percentage emphysema and HPX percentage ventilation correlation was also statistically significant (r = 0.695, p < 0.001). The whole lung HPX percentage ventilation correlated with the PFT measurements (FEV1 with r = - 0.886, p < 0.001*, and FEV1/FVC with r = - 0.861, p < 0.001*) better than the whole lung CT percentage emphysema score (FEV1 with r = - 0.635, p = 0.027; and FEV1/FVC with r = - 0.652, p = 0.021). CONCLUSION: Lobar ventilation with HPX-MRI showed a strong correlation with lobar ventilation and perfusion measurements derived from SPECT/CT, and is better than the emphysema score obtained with high-resolution CT. KEY POINTS: • The ventilation hyperpolarized xenon-129 MRI correlates well with ventilation and perfusion with SPECT/CT with the advantage of higher temporal and spatial resolution. • The hyperpolarized xenon-129 MRI correlates with the PFT measurements better than the high-resolution CT with the advantage of avoiding the use of ionizing radiation.

Factors predicting ablation site recurrence following percutaneous microwave ablation of colorectal hepatic metastases.

BACKGROUND: Microwave ablation (MWA) is a recognised treatment option for liver metastases. The size of the tumour is a well-established factor that influences the success of MWA. However, the effect of "heat sink" on the success of MWA for hepatic metastases is unclear. The aim of this study was to determine whether heat sink effect is a factor that contributes to ablation site recurrence (ASR). METHODS: A prospectively maintained database of patients who underwent percutaneous MWA for treatment of colorectal liver metastases was analysed. Imaging and demographic characteristics were compared between metastases that recurred following ablation and those that did not. Proximity to a large hepatic vein was defined as <10 mm. RESULTS: 126 ablations in 87 patients met the inclusion criteria and were studied over a median follow-up period of 28 (12-75) months. ASR was detected in 43 ablations (34%) and was associated with clinical risk score (CRS) ≥2 (OR 2.2 95% CI 1.3-3.3, p = 0.029), metastasis size (OR 0.953 95% CI (0.929-0.978), p < 0.001) and proximity to a large hepatic vein (OR 7.5 95%CI 2.4-22.8, p < 0.001). Proximity to a large hepatic vein was not associated with reduced overall survival (OS) but was associated with liver-specific recurrence (HR 4.7 95%CI 1.7-12.5, p = 0.004). CONCLUSIONS: In addition to tumour size proximity to large hepatic venous structures is an independent predictor of ASR and liver-specific recurrence following MWA. However, this was not associated with overall survival.

Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial.

BACKGROUND: Previous preclinical research has shown that extracorporeal devices can be used to enhance the delivery and distribution of systemically administered anticancer drugs, resulting in increased intratumoural concentrations. We aimed to assess the safety and feasibility of targeted release and enhanced delivery of doxorubicin to solid tumours from thermosensitive liposomes triggered by mild hyperthermia, induced non-invasively by focused ultrasound. METHODS: We did an open-label, single-centre, phase 1 trial in a single UK hospital. Adult patients (aged ≥18 years) with unresectable and non-ablatable primary or secondary liver tumours of any histological subtype were considered for the study. Patients received a single intravenous infusion (50 mg/m2) of lyso-thermosensitive liposomal doxorubicin (LTLD), followed by extracorporeal focused ultrasound exposure of a single target liver tumour. The trial had two parts: in part I, patients had a real-time thermometry device implanted intratumourally, whereas patients in part II proceeded without thermometry and we used a patient-specific model to predict optimal exposure parameters. We assessed tumour biopsies obtained before and after focused ultrasound exposure for doxorubicin concentration and distribution. The primary endpoint was at least a doubling of total intratumoural doxorubicin concentration in at least half of the patients treated, on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02181075, and is now closed to recruitment. FINDINGS: Between March 13, 2015, and March 27, 2017, ten patients were enrolled in the study (six patients in part I and four in part II), and received a dose of LTLD followed by focused ultrasound exposure. The treatment resulted in an average increase of 3·7 times in intratumoural biopsy doxorubicin concentrations, from an estimate of 2·34 µg/g (SD 0·93) immediately after drug infusion to 8·56 µg/g (5·69) after focused ultrasound. Increases of two to ten times were observed in seven (70%) of ten patients, satisfying the primary endpoint. Serious adverse events registered were expected grade 4 transient neutropenia in five patients and prolonged hospital stay due to unexpected grade 1 confusion in one patient. Grade 3-4 adverse events recorded were neutropenia (grade 3 in one patient and grade 4 in five patients), and grade 3 anaemia in one patient. No treatment-related deaths occurred. INTERPRETATION: The combined treatment of LTLD and non-invasive focused ultrasound hyperthermia in this study seemed to be clinically feasible, safe, and able to enhance intratumoural drug delivery, providing targeted chemo-ablative response in human liver tumours that were refractory to standard chemotherapy. FUNDING: Oxford Biomedical Research Centre, National Institute for Health Research.

Fast dynamic ventilation MRI of hyperpolarized 129 Xe using spiral imaging.

PURPOSE: To develop and optimize a rapid dynamic hyperpolarized 129 Xe ventilation (DXeV) MRI protocol and investigate the feasibility of capturing pulmonary signal-time curves in human lungs. THEORY AND METHODS: Spiral k-space trajectories were designed with the number of interleaves Nint = 1, 2, 4, and 8 corresponding to voxel sizes of 8 mm, 5 mm, 4 mm, and 2.5 mm, respectively, for field of view = 15 cm. DXeV images were acquired from a gas-flow phantom to investigate the ability of Nint = 1, 2, 4, and 8 to capture signal-time curves. A finite element model was constructed to investigate gas-flow dynamics corroborating the experimental signal-time curves. DXeV images were also carried out in six subjects (three healthy and three chronic obstructive pulmonary disease subjects). RESULTS: DXeV images and numerical modelling of signal-time curves permitted the quantification of temporal and spatial resolutions for different numbers of spiral interleaves. The two-interleaved spiral (Nint = 2) was found to be the most time-efficient to obtain DXeV images and signal-time curves of whole lungs with a temporal resolution of 624 ms for 13 slices. Signal-time curves were well matched in three healthy volunteers. The Spearman's correlations of chronic obstructive pulmonary disease subjects were statistically different from three healthy subjects (P < 0.05). CONCLUSION: The Nint = 2 spiral demonstrates the successful acquisition of DXeV images and signal-time curves in healthy subjects and chronic obstructive pulmonary disease patients. Magn Reson Med 79:2597-2606, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Chronic Obstructive Pulmonary Disease: Lobar Analysis with Hyperpolarized 129Xe MR Imaging.

Purpose To compare lobar ventilation and apparent diffusion coefficient (ADC) values obtained with hyperpolarized xenon 129 (129Xe) magnetic resonance (MR) imaging to quantitative computed tomography (CT) metrics on a lobar basis and pulmonary function test (PFT) results on a whole-lung basis in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods The study was approved by the National Research Ethics Service Committee; written informed consent was obtained from all patients. Twenty-two patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent hyperpolarized 129Xe MR imaging at 1.5 T, quantitative CT, and PFTs. Whole-lung and lobar 129Xe MR imaging parameters were obtained by using automated segmentation of multisection hyperpolarized 129Xe MR ventilation images and hyperpolarized 129Xe MR diffusion-weighted images after coregistration to CT scans. Whole-lung and lobar quantitative CT-derived metrics for emphysema and bronchial wall thickness were calculated. Pearson correlation coefficients were used to evaluate the relationship between imaging measures and PFT results. Results Percentage ventilated volume and average ADC at lobar 129Xe MR imaging showed correlation with percentage emphysema at lobar quantitative CT (r = -0.32, P < .001 and r = 0.75, P < .0001, respectively). The average ADC at whole-lung 129Xe MR imaging showed moderate correlation with PFT results (percentage predicted transfer factor of the lung for carbon monoxide [Tlco]: r = -0.61, P < .005) and percentage predicted functional residual capacity (r = 0.47, P < .05). Whole-lung quantitative CT percentage emphysema also showed statistically significant correlation with percentage predicted Tlco (r = -0.65, P < .005). Conclusion Lobar ventilation and ADC values obtained from hyperpolarized 129Xe MR imaging demonstrated correlation with quantitative CT percentage emphysema on a lobar basis and with PFT results on a whole-lung basis. © RSNA, 2016.

Imaging oligometastatic cancer before local treatment.

With the advent of novel treatment strategies to help widen the therapeutic window for patients with oligometastatic cancer, improved biomarkers are needed to reliably define patients who can benefit from these treatments. Multimodal imaging is one such option and should be optimised to comprehensively assess metastatic sites, disease burden, and response to neoadjuvant treatment in each disease setting. These features will probably remain important prognostic biomarkers, and are crucial in planning multidisciplinary treatment. There are opportunities to extract additional phenotypic information from conventional imaging, while novel imaging techniques can also reveal specific aspects of tumour biology. Imaging can both characterise and localise the phenotypic heterogeneity of multiple tumour sites. Novel approaches to existing imaging datasets and correlation with tumour biology will be important in realising the potential of imaging to guide treatment in the oligometastatic setting. In this Personal View, we discuss the current status and future directions of imaging before treatment in patients with extracranial oligometastases.