Paccione Eric N, Kwan Eugene, Bergquist Jake A, Shah Anish S, Orkild Ben A, Hunt Bram, Salter Maxwell L, Mendes Jason, DiBella Edward, Arai Andrew E, Bunch T Jared, MacLeod Rob S, Kunz Jeremy N, Hitchcock Ying, Kokeny Kristine E, Lloyd Shane, Ranjan Ravi
Nora Eccles Harrison Cardiovascular Research and Training Institute, The University of Utah, Salt Lake City, Utah; Department of Biomedical Engineering, The University of Utah, Salt Salt Lake City, Utah; Scientific Computing and Imaging Institute, The University of Utah, Salt Lake City, Utah.
Nora Eccles Harrison Cardiovascular Research and Training Institute, The University of Utah, Salt Lake City, Utah; Department of Biomedical Engineering, The University of Utah, Salt Salt Lake City, Utah.
Heart Rhythm. 2025 Jun 27. doi: 10.1016/j.hrthm.2025.06.041.
Although early studies of cardiac stereotactic body radiotherapy (cSBRT) show promise as a therapy to treat drug-refractory ventricular tachycardia, there remain knowledge gaps in its application, including the ideal doses to apply, which radiation source to use, which substrates to target, and the structural and electrophysiological effects seen after cSBRT.
Here, we examine doses up to 50 Gy to assess lesion formation by longitudinally following healthy myocardium after photon radiation using cardiac magnetic resonance (CMR) imaging and correlating those findings with histologic analysis.
Eight healthy canines underwent stereotactic photon beam cSBRT targeting healthy cardiac tissue. Serial CMR imaging assessed structural changes over time, imaging with late gadolinium enhancement, pre- and postcontrast T1, and precontrast T2 mapping. CMR images were registered to dosing plans, and left ventricular regions in 10 Gy increments from 0 to 50 Gy were identified for analysis. Histologic analysis was conducted postmortem to quantify fibrosis.
Scar-like late gadolinium enhancement intensity was observed only in regions receiving 40 to 50 Gy within 3 months after cSBRT but was confined to small relative volumes (<4% of target volume). T1 and extracellular volume values increased in a dose- and time-dependent manner, reaching physiological levels associated with diffuse fibrosis primarily with high doses yet present in low-dose regions. Histologic examination revealed a 102.7% relative increase (+0.38% absolute increase) in diffuse fibrosis in targeted regions compared with nonirradiated controls and a 34.41% relative increase (+0.19% absolute increase) in diffuse fibrosis in nontargeted regions at chronic time points (>90 days).
Photon cSBRT induces structural remodeling in healthy ventricular myocardium, primarily manifesting as diffuse remodeling that progressively increases with the radiation dose and the time interval after radiation without large areas of dense scar formation. These findings provide insight into the long-term effects of cSBRT, showing that healthy myocardium is unlikely to form large scar regions within 3 months and that diffuse remodeling should be further considered as a long-term effect of cSBRT.
尽管早期关于心脏立体定向体部放射治疗（cSBRT）的研究显示出有望成为治疗药物难治性室性心动过速的一种疗法，但在其应用方面仍存在知识空白，包括应用的理想剂量、使用哪种辐射源、靶向哪些底物以及cSBRT后观察到的结构和电生理效应。
在此，我们研究高达50 Gy的剂量，通过使用心脏磁共振（CMR）成像纵向跟踪光子辐射后健康心肌的情况来评估病变形成，并将这些发现与组织学分析相关联。
八只健康犬接受了针对健康心脏组织的立体定向光子束cSBRT。连续的CMR成像评估随时间的结构变化，采用延迟钆增强成像、对比剂前后T1成像以及对比剂前T2映射成像。CMR图像与剂量计划配准，并确定从0到50 Gy以10 Gy递增的左心室区域进行分析。死后进行组织学分析以量化纤维化。
仅在cSBRT后3个月内接受40至50 Gy照射的区域观察到类似瘢痕的延迟钆增强强度，但局限于相对较小的体积（<靶体积的4%）。T1和细胞外体积值以剂量和时间依赖的方式增加，主要在高剂量区域达到与弥漫性纤维化相关的生理水平，但在低剂量区域也存在。组织学检查显示与未照射对照相比，靶向区域弥漫性纤维化相对增加102.7%（绝对增加0.38%），在慢性时间点（>90天）非靶向区域弥漫性纤维化相对增加34.41%（绝对增加0.19%）。
光子cSBRT可诱导健康心室心肌发生结构重塑主要表现为弥漫性重塑，其随辐射剂量和辐射后时间间隔逐渐增加，且无大面积致密瘢痕形成。这些发现为cSBRT的长期效应提供了见解，表明健康心肌在3个月内不太可能形成大的瘢痕区域，且弥漫性重塑应进一步被视为cSBRT的长期效应。
