Cardiac MRI assessment of anthracycline-induced cardiotoxicity

Figures

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  FIGURE 1. Description of the automatic process to calculate left ventricular (LV) volume and strain. As shown, (A) the LV endocardium and epicardium are automatically contoured on the LV short axis slices. The mitral valve base plane is detected on the long axis slices of the left ventricle and projected onto the LV short axis slices. (B) To calculate the LV volumes, slices are stacked and contoured areas are summed up. At the same time, the mitral valve base plane is intersected with the stack of slices to remove portions of the volume that are above the base plane and inside the left atrium. From (38) with permission.

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  FIGURE 2. CMR end-diastole and end-systole frames from a cine loop for a 49-year-old breast cancer patient who experienced an associated LVEF decline from 61% at baseline (A) to 43% 3 months after anthracycline-based chemotherapy (B), which was measured using these CMR images. (A) Shows 4-chamber and 2-chamber view CMR imaging of the cancer patient pre-chemotherapy, and (B) shows CMR imaging of the same cancer patient 3 months after chemotherapy. (C) Shows the short-axis view tracing of the LV at end-diastole and at end-systole at baseline, which can be compared to (D) which shows short-axis view tracings of the LV at end-diastole and end-systole of this patient at 3 months after chemotherapy. In these tracings, the red tracing outlines the blood pool in the left ventricle, and the green tracing outlines the left ventricle. These tracings, which indicate LVEDV and LVESV, are used to calculate LVEF.

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  FIGURE 3. Six-month change in cardiovascular magnetic resonance (CMR)-derived left ventricular (LV) remodeling measurements after anthracycline-based chemotherapy. Six-month change in CMR-derived measurements of left ventricular remodeling in adults treated with anthracycline-based chemotherapy (Anth-bC, orange), non-Anth-bC (purple) for breast cancer or hematologic malignancy and cancer-free comparators of similar age (white). Compared with cancer-free comparators, those receiving Anth-bC had a significant decrease in LV ejection fraction (LVEF; A P < 0.01) and LV myocardial mass (B; P = 0.03) that occurred concurrently with increased end-systolic wall stress index (C; P < 0.01) and reduced ventricular-arterial coupling (D; P < 0.01). Changes among patients with cancer who received non–Anth-bC were not statistically different than those observed in non-cancer comparators (P > 0.15 for all). Data shown as mean ± SEM. *P < 0.05 for change from baseline. †P < 0.05 vs. change in control. From Jordan et al. (31) with permission.

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  FIGURE 4. Mid-wall circumferential myocardial strain measured with CMR in cancer patients prior to (BL) and 3 months (3M) after initiation of chemotherapy categorized by underlying cause for left ventricular ejection fraction (LVEF) decline. Participants with a decline in LVEF due to a > 5 ml decrease in end diastolic volume exhibited subclinical deteriorations in myocardial strain. Myocardial strain changes were not observed in any other subgroup, including those with end systolic volume changes. From Jordan et al. (37) with permission.

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  FIGURE 5. T1 and T2-mapping of the myocardium prior to anthracycline-based chemotherapy (A) and 3 months after anthracycline-based chemotherapy (B). T1 has changed, which indicates active injury or ongoing fibrosis. T2 has also changed, which indicates increased water and active inflammation of the myocardium.

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  FIGURE 6. Serial histograms of myocardial LGE signal intensity (top, mean intensity shown above the inverted black triangles) and corresponding histopathology (bottom) of individual animals 4 weeks after receipt of normal saline (left), doxorubicin without an LVEF drop (middle), and doxorubicin with an LVEF drop (right). Vacuolization (arrows) and increased extracellular space (dashed arrows) were observed in animals with doxorubicin cardiotoxicity. From Lightfoot et al. (53) with permission.

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  FIGURE 7. Comparison of T1 and ECV map images. Representative left ventricular (LV) short-axis native T1 (top row) and extracellular volume (ECV, bottom row) maps are shown in similarly aged participants. The LV and right ventricular (RV) blood pool cavities are noted. On each image, the color of pixels in the images (color scales on left) identifies the native T1 (milliseconds) and ECV (%). Insets on the ECV maps demonstrate the change in color intensity within the anterolateral wall of each ventricle. As shown, ECV is elevated in the cancer survivor previously treated with anthracycline-based chemotherapy. From Jordan et al. (56) with permission.

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  FIGURE 8. Cardiovascular magnetic resonance (CMR) assessments of myocardial T1. Myocardial native T1 of control participants without cancer (965 ± 3 ms) and cancer pretreatment participants (1,058 ± 7 ms) compared with cancer survivors treated with anthracycline chemotherapy (1,040 ± 7 ms). Myocardial T1 is elevated in both cancer groups, reflecting potential myocardial fibrosis compared with cancer-free control participants (P < 0.0001 for both). From Jordan et al. (56) with permission.

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  FIGURE 9. Cardiovascular magnetic resonance (CMR) assessments of myocardial extracellular volume (ECV). Myocardial ECV measured by cardiovascular magnetic resonance in controls (26.9 ± 0.2%) and cancer pretreatment participants (27.8 ± 0.7%) compared with cancer survivors treated with anthracycline chemotherapy (30.4 ± 0.7%). ECV incrementally increases across the groups (P< 0.0001) with a significant increase in post-treatment ECV values compared with pretreatment ECV values (P< 0.01). From Jordan et al. (56) with permission.

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  FIGURE 10. Study set-up with magnetic resonance imaging (MRI)-compatible exercise bike positioned in CMR imaging scanner. The subject, MRI scanner, MRI-compatible exercise bike, and ventilatory gas analysis are indicated by black arrows. The subject lies outside the MRI scanner and will pedal on an exercise bike as they move through the scanner. Ventilatory gas analysis is simultaneously performed while a cardiac MRI is obtained.

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  FIGURE 11. Cine image at rest. One image of a cine loop at the end short-axis view of the myocardium. The left ventricle is gray, while the blood pool is white. At rest, the workload is 0 w, and the patient’s heart rate is 50 bpm and respiratory rate is 11 breaths/min.

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  FIGURE 12. Cine image during exercise. One image of cine loop at the end short-axis view of the myocardium. The left ventricle is gray, while the blood pool is white. During exercise, the workload is 110 w, and the patient’s heart rate is 101 bpm and respiratory rate is 21 breaths/min.