PMID- 33400646
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20240402
IS  - 1558-2531 (Electronic)
IS  - 0018-9294 (Print)
IS  - 0018-9294 (Linking)
VI  - 68
IP  - 6
DP  - 2021 Jun
TI  - A Theoretical Argument for Extended Interpulse Delays in Therapeutic 
      High-Frequency Irreversible Electroporation Treatments.
PG  - 1999-2010
LID - 10.1109/TBME.2021.3049221 [doi]
AB  - High-frequency irreversible electroporation (H-FIRE) is a tissue ablation 
      modality employing bursts of electrical pulses in a positive phase-interphase 
      delay (d(1))-negative phase-interpulse delay (d(2)) pattern. Despite accumulating 
      evidence suggesting the significance of these delays, their effects on 
      therapeutic outcomes from clinically-relevant H-FIRE waveforms have not been 
      studied extensively. OBJECTIVE: We sought to determine whether modifications to 
      the delays within H-FIRE bursts could yield a more desirable clinical outcome in 
      terms of ablation volume versus extent of tissue excitation. METHODS: We used a 
      modified spatially extended nonlinear node (SENN) nerve fiber model to evaluate 
      excitation thresholds for H-FIRE bursts with varying delays. We then calculated 
      non-thermal tissue ablation, thermal damage, and excitation in a clinically 
      relevant numerical model. RESULTS: Excitation thresholds were maximized by 
      shortening d(1), and extension of d(2) up to 1,000 mus increased excitation 
      thresholds by at least 60% versus symmetric bursts. In the ablation model, long 
      interpulse delays lowered the effective frequency of burst waveforms, modulating 
      field redistribution and reducing heat production. Finally, we demonstrate 
      mathematically that variable delays allow for increased voltages and larger 
      ablations with similar extents of excitation as symmetric waveforms. CONCLUSION: 
      Interphase and interpulse delays play a significant role in outcomes resulting 
      from H-FIRE treatment. SIGNIFICANCE: Waveforms with short interphase delays 
      (d(1)) and extended interpulse delays (d(2)) may improve therapeutic efficacy of 
      H-FIRE as it emerges as a clinical tissue ablation modality.
FAU - Aycock, Kenneth N
AU  - Aycock KN
FAU - Zhao, Yajun
AU  - Zhao Y
FAU - Lorenzo, Melvin F
AU  - Lorenzo MF
FAU - Davalos, Rafael V
AU  - Davalos RV
LA  - eng
GR  - P30 CA012197/CA/NCI NIH HHS/United States
GR  - R01 CA240476/CA/NCI NIH HHS/United States
GR  - P01 CA207206/CA/NCI NIH HHS/United States
GR  - R43 CA233158/CA/NCI NIH HHS/United States
GR  - R01 CA213423/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210521
PL  - United States
TA  - IEEE Trans Biomed Eng
JT  - IEEE transactions on bio-medical engineering
JID - 0012737
SB  - IM
MH  - *Electroporation
PMC - PMC8291206
MID - NIHMS1707306
EDAT- 2021/01/06 06:00
MHDA- 2021/06/29 06:00
PMCR- 2022/06/01
CRDT- 2021/01/05 17:10
PHST- 2021/01/06 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/01/05 17:10 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 10.1109/TBME.2021.3049221 [doi]
PST - ppublish
SO  - IEEE Trans Biomed Eng. 2021 Jun;68(6):1999-2010. doi: 10.1109/TBME.2021.3049221. 
      Epub 2021 May 21.