Quantitative Analysis of Radiation Therapy-Induced Cardiac and Aortic Sequelae in Patients With Lung Cancer via Magnetic Resonance Imaging: A Pilot Study.

PURPOSE: The objective of this study was to quantify early radiation therapy (RT)-induced cardiac and aortic changes in patients with lung cancer using cardiac magnetic resonance imaging (MRI). METHODS AND MATERIALS: Nine patients with lung cancer treated with RT completed MR scans at baseline (before RT) and at 3 and 6 months after RT completion. Cine, T1/T2, late gadolinium enhancement (LGE), and 4-dimensional flow MRIs were acquired to assess biological and mechanical cardiovascular changes globally (ie, over the entire left ventricle (LV) or aorta) and regionally (according to an American Heart Association model). RESULTS: Regional metrics demonstrated multiple significant changes and dose-dependent responses. Notably, LGE showed changes at 3 and 6 months over septal and high-dose regions (P < .0458). Longitudinal strain changes were notable at septal and high-dose regions at 3 months and at septal regions at 6 months (P < .0469). Elevated T1/T2 signals (P < .0391) and changes in radial/circumferential strain at the septum (P < .0391) were observed at 3 months. Both T1/T2 signal and LGE were correlated with dose at 6 months (T1 signal also at 3 months), with significantly greater changes in regions receiving >50 Gy (P < .0331). LV dose was not correlated with LV strain changes (P > .1), but ascending aortic dose was correlated with strain changes at segments 1 and 2 of the LV (P < .0362). Global metrics identified only 2 significant responses: increase in LGE volume at 6 months and a reduction in ascending aortic circumferential strain at 3 months (P < .0356). CONCLUSIONS: Early MR-based changes after RT occurred primarily in high-dose regions and the LV septal wall. Although several early signals resolved by 6 months, LGE and longitudinal strain changes persisted for at least 6 months. Dose-dependent responses/correlations were observed for T1/T2/LGE changes at 6 months, with the greatest effect in regions exposed to >50 Gy. Further investigations with larger cohorts and longer follow-up are warranted to confirm regional dose dependence and the association between aortic dose and LV strain observed in this pilot study.

Quantitative assessment of radiotherapy-induced myocardial damage using MRI: a systematic review.

PURPOSE: To determine the role of magnetic resonance imaging (MRI)-based metrics to quantify myocardial toxicity following radiotherapy (RT) in human subjects through review of current literature. METHODS: Twenty-one MRI studies published between 2011-2022 were identified from available databases. Patients received chest irradiation with/without other treatments for various malignancies including breast, lung, esophageal cancer, Hodgkin's, and non-Hodgkin's lymphoma. In 11 longitudinal studies, the sample size, mean heart dose, and follow-up times ranged from 10-81 patients, 2.0-13.9 Gy, and 0-24 months after RT (in addition to a pre-RT assessment), respectively. In 10 cross-sectional studies, the sample size, mean heart dose, and follow-up times ranged from 5-80 patients, 2.1-22.9 Gy, and 2-24 years from RT completion, respectively. Global metrics of left ventricle ejection fraction (LVEF) and mass/dimensions of cardiac chambers were recorded, along with global/regional values of T1/T2 signal, extracellular volume (ECV), late gadolinium enhancement (LGE), and circumferential/radial/longitudinal strain. RESULTS: LVEF tended to decline at >20 years follow-up and in patients treated with older RT techniques. Changes in global strain were observed after shorter follow-up (13±2 months) for concurrent chemoradiotherapy. In concurrent treatments with longer follow-up (8.3 years), increases in left ventricle (LV) mass index were correlated with LV mean dose. In pediatric patients, increases in LV diastolic volume were correlated with heart/LV dose at 2 years post-RT. Regional changes were observed earlier post-RT. Dose-dependent responses were reported for several parameters, including: increased T1 signal in high-dose regions, a 0.136% increase of ECV per Gy, progressive increase of LGE with increasing dose at regions receiving >30 Gy, and correlation between increases in LV scarring volume and LV mean/V10/V25 Gy dose. CONCLUSION: Global metrics only detected changes over longer follow-up, in older RT techniques, in concurrent treatments, and in pediatric patients. In contrast, regional measurements detected myocardial damage at shorter follow-up and in RT treatments without concurrent treatment and had greater potential for dose-dependent response. The early detection of regional changes suggests the importance of regional quantification of RT-induced myocardial toxicity at early stages, before damage becomes irreversible. Further works with homogeneous cohorts are required to examine this matter.

Effects of respiratory and cardiac motion on estimating radiation dose to the left ventricle during radiotherapy for lung cancer.

PURPOSE: Establish a workflow to evaluate radiotherapy (RT) dose variation induced by respiratory and cardiac motion on the left ventricle (LV) and left ventricular myocardium (LVM). METHODS: Eight lung cancer patients underwent 4D-CT, expiratory T1-volumetric-interpolated-breath-hold-examination (VIBE), and cine MRI scans in expiration. Treatment plans were designed on the average intensity projection (AIP) datasets from 4D-CTs. RT dose from AIP was transferred onto 4D-CT respiratory phases. About 50% 4D-CT dose was mapped onto T1-VIBE (following registration) and from there onto average cine MRI datasets. Dose from average cine MRI was transferred onto all cardiac phases. Cumulative cardiac dose was estimated by transferring dose from each cardiac phase onto a reference cine phase following deformable image registration. The LV was contoured on each 4D-CT breathing phase and was called clinical LV (cLV); this structure is blurred by cardiac motion. Additionally, LV, LVM, and an American Heart Association (AHA) model were contoured on all cardiac phases. Relative maximum/mean doses for contoured regions were calculated with respect to each patient's maximum/mean AIP dose. RESULTS: During respiration, relative maximum and mean doses on the cLV ranged from -4.5% to 5.6% and -14.2% to 16.5%, respectively, with significant differences in relative mean doses between inspiration and expiration (P < 0.0145). During cardiac motion at expiration, relative maximum and mean doses on the LV ranged from 1.6% to 59.3%, 0.5% to 27.4%, respectively. Relative mean doses were significantly different between diastole and systole (P = 0.0157). No significant differences were noted between systolic, diastolic, or cumulative cardiac doses compared to the expiratory 4D-CT (P > 0.14). Significant differences were observed in AHA segmental doses depending on tumour proximity compared to global LV doses on expiratory 4D-CT (P < 0.0117). CONCLUSION: In this study, the LV dose was highest during expiration and diastole. Segmental evaluation suggested that future cardiotoxicity evaluations may benefit from regional assessments of dose that account for cardiopulmonary motion.

Quantitative assessment of intra- and inter-modality deformable image registration of the heart, left ventricle, and thoracic aorta on longitudinal 4D-CT and MR images.

PURPOSE: Magnetic resonance imaging (MRI)-based investigations into radiotherapy (RT)-induced cardiotoxicity require reliable registrations of magnetic resonance (MR) imaging to planning computed tomography (CT) for correlation to regional dose. In this study, the accuracy of intra- and inter-modality deformable image registration (DIR) of longitudinal four-dimensional CT (4D-CT) and MR images were evaluated for heart, left ventricle (LV), and thoracic aorta (TA). METHODS AND MATERIALS: Non-cardiac-gated 4D-CT and T1 volumetric interpolated breath-hold examination (T1-VIBE) MRI datasets from five lung cancer patients were obtained at two breathing phases (inspiration/expiration) and two time points (before treatment and 5 weeks after initiating RT). Heart, LV, and TA were manually contoured. Each organ underwent three intramodal DIRs ((A) CT modality over time, (B) MR modality over time, and (C) MR contrast effect at the same time) and two intermodal DIRs ((D) CT/MR multimodality at same time and (E) CT/MR multimodality over time). Hausdorff distance (HD), mean distance to agreement (MDA), and Dice were evaluated and assessed for compliance with American Association of Physicists in Medicine (AAPM) Task Group (TG)-132 recommendations. RESULTS: Mean values of HD, MDA, and Dice under all registration scenarios for each region of interest ranged between 8.7 and 16.8 mm, 1.0 and 2.6 mm, and 0.85 and 0.95, respectively, and were within the TG-132 recommended range (MDA < 3 mm, Dice > 0.8). Intramodal DIR showed slightly better results compared to intermodal DIR. Heart and TA demonstrated higher registration accuracy compared to LV for all scenarios except for HD and Dice values in Group A. Significant differences for each metric and tissue of interest were noted between Groups B and D and between Groups B and E. MDA and Dice significantly differed between LV and heart in all registrations except for MDA in Group E. CONCLUSIONS: DIR of the heart, LV, and TA between non-cardiac-gated longitudinal 4D-CT and MRI across two modalities, breathing phases, and pre/post-contrast is acceptably accurate per AAPM TG-132 guidelines. This study paves the way for future evaluation of RT-induced cardiotoxicity and its related factors using multimodality DIR.

Global epidemic trend of tuberculosis during 1990-2010: using segmented regression model.

BACKGROUND: Tuberculosis (TB) is a pandemic disease. It is the second leading cause of death from infectious diseases after human immunodeficiency virus (HIV) in the world.The main objective of this paper was to determine and compare the epidemiology of TB incidence rate and its trend changes during 1990-2010 in six WHO regions regarding age, gender and income levels. METHODS: The Average Annual Percent Change (AAPC) and Annual Percent Change (APC) of TB incidence, mortality, treatment-successes, case detection rates, as well as change points of trend was estimated using segmented regression model. The number of change points was selected by the permutation procedure based on likelihood ratio test. RESULTS: Two change points for global TB incidence rate trend with AAPC5years equaling -1.4 % was estimated, the maximum AAPC5years of six regions was attributed to the American region (-3.5%). AACP of TB treatment-successes rate for Eastern Mediterranean (+2.2), the Americas (+1.6), south East Asia (+.8) and Global (+1.1) were significant (P<0.05). Moreover AACP5years of TB case detection rate for South East Asia (+7.5), Eastern Mediterranean (+4.9), Africa (+2.8) and the Americas (+1.7) were significant (P<0.05). Globally, all of income categories had descending trend of TB incidence and mortality rate, except the upper-middle income level that had ascending incidence trend (AAPC=+0.7%). CONCLUSIONS: Globally, TB incidence and mortality rates have downturn trend and TB treatment successes and detection rates have upward trend, but their changes rate are insufficient to reach the goal of TB stop strategy. The economic levels have effect on trend, with no clear pattern, so it seems necessary that evaluation TB control programs based on characteristics of countries for reach TB control goals.