Precision in iterative modulation enhanced single-molecule localization microscopy

Journal article (2022)

Authors

D. Kalisvaart Team Carlas Smith - Mechanical, Maritime and Materials Engineering
J.P. Cnossen Team Carlas Smith - Mechanical, Maritime and Materials Engineering
S. Hung Team Carlas Smith - Mechanical, Maritime and Materials Engineering
S. Stallinga ImPhys/Imaging Physics
Sjoerd Stallinga ImPhys/Imaging Physics
M.H.G. Verhaegen Team Michel Verhaegen - Mechanical, Maritime and Materials Engineering
C.S. Smith Team Carlas Smith - Mechanical, Maritime and Materials Engineering , ImPhys/Computational Imaging - AS
Research Group
Team Carlas Smith (Mechanical, Maritime and Materials Engineering) (TU Delft)
Copyright: © 2022 D. Kalisvaart, J.P. Cnossen, S. Hung, S. Stallinga, M.H.G. Verhaegen, C.S. Smith
DOI: https://doi.org/10.1016/j.bpj.2022.05.027
More Info
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Published Date

2022

Language

English

Faculty

Mechanical, Maritime and Materials Engineering

Department

Delft Center for Systems and Control

Research Group

Team Carlas Smith

Abstract

Modulation enhanced single-molecule localization microscopy (meSMLM) methods improve the localization precision by using patterned illumination to encode additional position information. Iterative meSMLM (imeSMLM) methods iteratively generate prior information on emitter positions, used to locally improve the localization precision during subsequent iterations. The Cramér-Rao lower bound cannot incorporate prior information to bound the best achievable localization precision because it requires estimators to be unbiased. By treating estimands as random variables with a known prior distribution, the Van Trees inequality (VTI) can be used to bound the best possible localization precision of imeSMLM methods. An imeSMLM method is considered, where the positions of in-plane standing-wave illumination patterns are controlled over the course of multiple iterations. Using the VTI, we analytically approximate a lower bound on the maximum localization precision of imeSMLM methods that make use of standing-wave illumination patterns. In addition, we evaluate the maximally achievable localization precision for different illumination pattern placement strategies using Monte Carlo simulations. We show that in the absence of background and under perfect modulation, the information content of signal photons increases exponentially as a function of the iteration count. However, the information increase is no longer exponential as a function of the iteration count under non-zero background, imperfect modulation, or limited mechanical resolution of the illumination positioning system. As a result, imeSMLM with two iterations reaches at most a fivefold improvement over SMLM at 8 expected background photons per pixel and 95% modulation contrast. Moreover, the information increase from imeSMLM is balanced by a reduced signal photon rate. Therefore, SMLM outperforms imeSMLM when considering an equal measurement time and illumination power per iteration. Finally, the VTI is an excellent tool for the assessment of the performance of illumination control and is therefore the method of choice for optimal design and control of imeSMLM methods.