Improved imaging interfaces on a co-registered ultrasound and optical microscopy multiscale system - Research paper

Q: What problem does the paper address in co-registered ultrasound and optical microscopy?

It addresses degraded ultrasound image quality near the optical window caused by off-axis acoustic noise (clutter), particularly at the glass optical window.

Q: How did the researchers reduce acoustic clutter near the optical window?

They tested multiple optical window materials and paired them with different ultrasound beamforming techniques, varying focal configurations and using acoustic coupling beneath the window.

Q: What were the key findings regarding the optical window materials?

COC and Ibidi® optical windows significantly improved ultrasound image quality by reducing acoustic clutter by more than 40% compared with glass, while maintaining comparable MPM quality based on SHG PSF and collagen alignment errors under 5%.

Sep 29, 2026

Upload by Connor

Integrating ultrasound with multiphoton microscopy enables comprehensive tissue characterization by combining contrast mechanisms across spatial scales, but degraded ultrasound quality occurs at the glass optical window due to off-axis acoustic noise. This study reduces window-related clutter by testing different optically clear window materials together with varied ultrasound beamforming approaches, including focused configurations and acoustic coupling beneath the window. Ultrasound B-mode clutter was quantified and MPM performance assessed using SHG PSF measurements, along with collagen alignment quantification in rat tail tendon samples and collagen gels.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Abstract

Introduction

Multiscale multimodal tissue imaging

Correlative MPM and high-frequency ultrasound system

RESEARCH PAPER Improved imaging interfaces on a co-registered ultrasound and optical microscopy multiscale system Jonathan Hale ,a Nathan Cudworth,a Renata Farrell ,b Aarushi Bhargava ,a,b Kevin W. Eliceiri ,a,b,* and Ivan Rosado-Mendeza,c,* aUniversity of Wisconsin–Madison, School of Medicine and Public Health, Department of Medical Physics, Madison, Wisconsin, United States bUniversity of Wisconsin–Madison, College of Engineering, Department of Biomedical Engineering, Madison, Wisconsin, United States cUniversity of Wisconsin–Madison, School of Medicine and Public Health, Department of Radiology, Madison, Wisconsin, United States ABSTRACT. Significance: Integrating ultrasound (US) with multiphoton microscopy (MPM) enables comprehensive tissue characterization by combining contrast mechanisms across spatial scales. However, prior implementations suffer from degraded US image quality at the glass optical window arising from off-axis acoustic noise (clutter) . Aim: We aimed to reduce clutter near the optical window without compromising the MPM image quality using different optical window materials combined with different ultrasound beamforming techniques. Approach: Clutter in B-mode images was measured for glass and several optically clear polymer films using physically or synthetically focused US beamforming with varied focal configurations (f∕\#) and with acoustic coupling beneath the window. MPM image quality with the material optical windows was assessed via second harmonic generation (SHG) point spread function (PSF) measurements. We evaluated SHG-based automated collagen fiber alignment quantification with the optical windows in rat tail tendon samples and collagen gels. Results: Candidate materials included polymethyl pentene (PMP), cyclin olefin copolymer (COC), polycarbonate (PC), polyethylene terephthalate, polymethyl methacrylate, and an Ibidi® polymer coverslip. At receive f∕\# ≥ 2, COC and Ibidi® reduced acoustic clutter by >40% compared with glass with physical focusing regardless of physically or synthetically focused beams or acoustic coupling. Collagen gel imaged with COC and high f∕\# showed clearer ultrasound speckle close to the optical windows. COC, Ibidi®, PMP, and PC showed minimal SHG PSF differences from glass and collagen alignment errors <5% relative to glass. Conclusions: COC or Ibidi® optical windows significantly improve US image quality without compromising MPM quality. These enhancements support future multimodal studies with high-quality, co-registered US and MPM data. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. [DOI: 10.1117/1.JBO.31.1.016002] Keywords: nonlinear optics; second-harmonic generation; multiscale; multimodal; ultrasound; acoustic clutter; collagen Paper 250246GR received Aug. 14, 2025; revised Nov. 19, 2025; accepted Nov. 20, 2025; published Dec. 25, 2025 . *Address all correspondence to Kevin W. Eliceiri, [eliceiri@wisc.edu](eliceiri@wisc.edu); Ivan Rosado-Mendez, [rosadomendez@wisc.edu](rosadomendez@wisc.edu) Journal of Biomedical Optics 016002-1 January 2026 • Vol. 31(1) Hale et al.: Improved imaging interfaces on a co-registered ultrasound and optical. . . 1 Introduction The combination of tissue imaging at different spatial scales can unveil the mechanisms by which macroscopic changes (several millimeters to centimeters) result from tissue remodeling at the nano- or micro-scales. Multimodal imaging can also overcome the limitations of individual modalities by building on the strengths of each other. For example, ultrasound imaging at diagnostic frequencies (1 to 30 MHz) can overcome the limiting penetration of optical imaging, whereas the latter allows for visualization of micro-scale structures that ultrasound cannot resolve. Moreover, a dir

FAQs

What problem does the paper address in co-registered ultrasound and optical microscopy?

It addresses degraded ultrasound image quality near the optical window caused by off-axis acoustic noise (clutter), particularly at the glass optical window.

How did the researchers reduce acoustic clutter near the optical window?

They tested multiple optical window materials and paired them with different ultrasound beamforming techniques, varying focal configurations and using acoustic coupling beneath the window.

What were the key findings regarding the optical window materials?

COC and Ibidi® optical windows significantly improved ultrasound image quality by reducing acoustic clutter by more than 40% compared with glass, while maintaining comparable MPM quality based on SHG PSF and collagen alignment errors under 5%.

Sep 29, 2026

Upload by Connor