Poster 134 - Quantifying Regional Perfusion Alterations Induced by High Versus Low Radiation Doses and Their Correlation with Left Ventricle Ejection Fraction in Breast Cancer Patients

Saturday, October 26, 2024

10:00 AM - 12:00 PM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Maia Gueron (she/her/hers)

Student Researcher in the MIACA Lab of the Radiation Oncology Department
University of Florida
Miami, Florida, United States

Co-Author(s)

Arjun Suresh

Student Researcher in MIACA Lab, Radiation Oncology Department
University of Florida
Lithia, Florida, United States

Primary Investigator(s)

Walter O'Dell, PhD

Associate Professor, Department of Radiation Oncolgy, College of Medicine
University of Florida, Florida, United States

Introduction: In 2024, approximately 310,720 women in the U.S. will be diagnosed with invasive breast cancer, making it the most prevalent cancer among women [1]. Advances in treatment, such as radiation therapy (RT), have led to a 39% reduction in mortality rates from 1990 to 2015 [2]. Despite these improvements, RT is associated with an increased risk of cardiac complications, including a 6.4-7% higher relative risk of major cardiac events [3]. Cardiac injury from RT often emerges years later, highlighting the need for early detection of cardiac damage.
This study aims to investigate the impact of RT on cardiac health by focusing on three main objectives: identifying the heart regions receiving the highest and lowest radiation doses, quantifying changes in cardiac perfusion in these regions, and evaluating how these changes relate to left ventricular ejection fraction (LVEF). Myocardial perfusion imaging, particularly through cardiac magnetic resonance imaging (CMRI), provides detailed insights into changes in blood flow and is less invasive compared to other imaging techniques [4]. Additionally, LVEF is crucial for assessing heart function and diagnosing heart failure.
The impact of this research on society is significant, as it aims to enhance the safety and effectiveness of breast cancer treatments by reducing the risk of long-term cardiac complications. By identifying how different radiation doses affect cardiac health, the study seeks to improve treatment planning and patient outcomes, ultimately contributing to better quality of life for breast cancer survivors.

Materials and

Methods: Perfusion imaging involved three short-axis CMRI slices, each with 50 images per heartbeat. Specialized software from Dr. O’Dell’s lab, based on NIH ImageJ, was employed to assess myocardial perfusion.
Manual segmentation of endocardial and epicardial borders was performed using contour tools. The software aligned each image to a reference time through manual and automated adjustments, correcting for heart movement and ensuring consistent analysis. Three regions of the heart wall were examined with color-coded calculation points to measure regional changes precisely.
Pixel intensity changes were calculated and plotted as uptake curves for myocardial perfusion. A logistic function modeled the sigmoidal nature of these curves, and time to the midpoint of the uptake curve was determined. Statistical significance between perfusion levels in different regions was assessed using a paired Student's t-test.
Radiation dose distribution was mapped from 3D dose data acquired from treatment plans and integrated with myocardial perfusion data. Planning CT scans referenced dose distributions, processed with custom ImageJ code. Axial MRI was aligned with CT to accurately overlay radiation dose information onto perfusion MRI slices, allowing analysis of radiation dose effects on myocardial perfusion and comparisons between high and low radiation exposure regions.
To assess LVEF, the LV endocardial border from end-diastole to end-systole was segmented in multiple image slices by three readers blinded to treatment modality. Conformal 3D models of the LV endocardial geometry provided precise LVEF estimates. Desmos was used to graph LVEF versus perfusion delay to analyze their relationship.

Results, Conclusions, and Discussions:

Results:
Analysis of the radiation doses across myocardial regions shows substantial variability. As demonstrated in Table 1, Region 2 in Slice 2 received the highest average dose of 43.405 Gy, while Region 0 in Slice 0 received the lowest dose of 0.146 Gy. The radiation doses increased progressively from Slice 0 to Slice 2. In terms of perfusion changes, it is revealed that there is a statistically significant difference (p = 0.0133) between high-dose (Slice 2, Region 2) and low-dose (Slice 0, Region 0) regions. High-dose regions consistently showed positive values for changes in perfusion delay, indicating a delay in perfusion post-radiation. In contrast, low-dose regions exhibited more variable perfusion changes.
Discussions:
Our data confirm that regional radiation exposure significantly affects regional perfusion, supporting our initial hypothesis. Table 2 demonstrates a clear statistical significance in perfusion delay between high-dose and low-dose regions, underscoring the impact of radiation on myocardial perfusion.
Figure 1 depicts a mild positive relationship between perfusion delay and left ventricular ejection fraction (LVEF). This suggests that as perfusion delay increases, overall heart function, as measured by LVEF, may decrease. This trend does not support our hypothesis that increased perfusion delay correlates with lower overall heart function.

Conclusions:
Regional changes in heart wall perfusion were measured using MRI in breast cancer patients 6-9 months after radiation treatment. A significant correlation was found between radiation dose exposure and changes in myocardial perfusion, indicating that radiation dose has a measurable impact on perfusion. Additionally, when evaluating overall heart function, a weak association was observed between the greatest regional perfusion change and LVEF. This suggests that while perfusion changes are notable, their direct effect on overall heart function is relatively minor.
The findings highlight that measurable alterations in myocardial perfusion and overall heart function can occur early after cancer treatment in breast cancer patients. This underscores the importance of ongoing cardiac monitoring in this population. To gain a clearer understanding of how radiation affects heart function and to identify patients needing more intensive follow-up, further research with larger patient cohorts is essential.

Acknowledgements (Optional):

References (Optional): [1] Akram, M., Iqbal, M., Daniyal, M., & Khan, A. U. (2017, October 2). Awareness and current knowledge of breast cancer - biological research. BioMed Central. https://biolres.biomedcentral.com/articles/10.1186/s40659-017-0140-9
[2] Gangnon, R. E., Stout, N. K., Alagoz, O., Hampton, J. M., Sprague, B. L., & Trentham-Dietz, A. (2018, April). Contribution of breast cancer to overall mortality for US women. Medical decision making: an international journal of the Society for Medical Decision Making. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963706/
[3] Wang, S., Tsai, W., Lin, K., Yu, C., Yang, S., Shueng, P., Wu, Y., Hsu, C., & Wu, T. (2023). Integrating subvolume dose and myocardial perfusion imaging parameters to assess the impact of radiation therapy on heart function in breast cancer patients: A comparative analysis between left‐ and right‐sided breast cancer. Thoracic Cancer, 14(26), 2696–2706. https://doi.org/10.1111/1759-7714.15056
[4] Ibrahim, M. A. (2023, July 3). Gadolinium Magnetic Resonance Imaging. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK482487/