Transcranial histotripsy parameter study in primary and metastatic murine brain tumor models

Autor: Sarah Duclos, Andrew Golin, Adam Fox, Neeraj Chaudhary, Sandra Camelo-Piragua, Aditya Pandey, Zhen Xu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Hyperthermia, Vol 40, Iss 1 (2023)
Druh dokumentu: article
ISSN: 02656736
1464-5157
0265-6736
DOI: 10.1080/02656736.2023.2237218
Popis: AbstractObjective This study investigated the effect of various histotripsy dosages on tumor cell kill and associated bleeding in two murine brain tumor models (glioma [Gl261] and lung metastasis [LL/2-Luc2]).Methods and materials GL261 or LL/2-Luc2 cells were cultured and implanted into the brains of C57BL/6 mice. Histotripsy (1-cycle pulses, 5 Hz PRF, 30 MPa-P) was performed using a 1 MHz transducer for five different dosages for each cell line: 5, 20 or 200 pulses per location (PPL) at a single treatment point, or 5 or 10–20 PPL at multiple treatment points. MRI, bioluminescence imaging and histology were used to assess tumor ablation and treatment effects within 4–6 h post-treatment.Results All treatment groups resulted in a reduction of BLI intensity for the LL/2-Luc2 tumors, with significant signal reductions for the multi-point groups. The average pre-/post-treatment BLI flux (photons/s, ×108) for the different treatment groups were: 4.39/2.19 (5 PPL single-point), 5.49/1.80 (20 PPL single-point), 3.86/1.73 (200 PPL single-point), 2.44/1.11 (5 PPL multi-point) and 5.85/0.80 (10 PPL multi-point). MRI and H&E staining showed increased tumor damage and hemorrhagic effects with increasing histotripsy dose for both GL261 and LL/2-Luc2 tumors, but the increase in tumor damage was diminished beyond 10–20 PPL for single-point treatments and outweighed by increased hemorrhage. In general, hemorrhage was confined to be within 1 mm of the treatment boundary for all groups.Conclusions Our results suggest that a lower number of histotripsy pulses at fewer focal locations can achieve substantial tumor kill while minimizing hemorrhage.
Databáze: Directory of Open Access Journals
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