Form 1

2019 Report Form for Collaboration with
Research Center for Biomedical Engineering

Year/month/dateP-2068

NumberDate /Month/Year
date: 25/03/2020

To Chairman, Board of Directors, Research Center for Biomedical Engineering

Affiliation
Title
NameAddress

ApplicantLinköping University, SwedenAssistant Professor
Rolf B Saager
Institutionen för medicinsk teknik (IMT),Linköping University,Plan 12, Campus US, SE-582 28

Phone
Fax
E-mail+46 13-28 67 62
Nonerolf.saager@liu.se
Report Form for Collaboration Research

Research Theme

Research AreaResearch Period（和） 迅速な非接触外傷評価のための臨床用カメラの設計（English） Clinical Imager Design for Rapid, Non-contact Wound Assessment
1. Biomaterials
2. Bioengineering
3. Functional molecules
4. Chemistry/Electrical Engineering/Mechanical Engineering/Materials Science

From:Date/month/Year
01/ 06/2019

To: Date/month/Year
31/ 03/2020

Applicant Organization
Name
Rolf B Saager
Nandan K Das

Collaboration Partners
Research CenterDepartment
Biomedical Engineering, Linkoping Univ.
SwedenBiomedical Engineering, Linkoping Univ.
SwedenintheTitle
Asst. Professor
Post-Doctoral
Scholar

Role
Project mgmt.
Spectral analysis
Integration,
System testing

Keiichiro Kagawa (Associate Professor, Research Institute ofElectronics, Shizuoka University)

Research Results (Including Purpose, Results, Figures, etc.)

Purpose: The purpose of this project in the 1-st year is the fabrication of a spectrally optimized compact
Spatial Frequency Domain Imaging (SFDI) device that will enable the rapid, wide-field quantification ofmultiple physiologic parameters in depth, critical to addressing unmet needs in burn severity assessment andwound healing. A compact compound eye camera developed at Shizuoka University is utilized as a key
device. The primary method of determining burn severity is subjective visual assessment. Its accuracy, evenby experts in the field, is only 60–80%. SFDI has the potential to non-invasively segment tissue, based on
both functional and structural tissue parameters specific to burn physiology; thereby establish a noncontact
method for quantifying clinical burn depth. Spatial Frequency Domain Spectroscopy (SFDS), and adaptationof SFDI, was invented and developed at UCI by the PI to enable high spectral resolution, depth-specific,quantitative tissue spectroscopy. The most significant limitation of our current SFDS system is that it can
only measure tissue at a single location at a time. Whereas this “point-spectroscopy” SFDS system has
demonstrated depth sensitive quantification of in vivo optical properties, both burns and their subsequent
wound healing will also present differential responses in lateral spatial extent.
Method: Figure 1a shows the two primary optical components of the proposed compact burn assessment
device: a projector and a multi-spectral compound eye camera with 9 bandpass filters that will enable
simultaneous spectral imaging over the same field of view. An optimized multi-spectral compound eyecamera (Shizuoka University) will detect remitted light. As this compound eye design affords us theopportunity to customize the spectral bands and their widths through the selection of either commerciallyavailable interference filters or through custom bandpass filter designs, the key element for success is themethod by which this selection is made. Figure 1b shows the physical layout of this compact device, with thecompound eye camera positioned above the compact micro-projector unit. The hand holding this systemgives a reference to the compact size of this integrated device.

Wide-band
illumination

TissuesSinusoidal
pattern projection

Fig. 1. Concept of compact SFDI device.
Results: As we have data on burn wounds in a preclinical study of 30 animals, collected by SFDS, we havethe basis from which to determine the 9 most significant spectral bands related to burn wound assessment
and design the senor around these application specific needs. In the design of compound eye camera
prototype, commercially available filters were used, which limited the overall performance. However, thisscheme was cost-efficient. Figure 2 shows a prototype multi-spectral camera (without filters in the photo)and filter assignment. A global-shutter CMOS image sensor with enhanced near-infrared (NIR) lightsensitivity was utilized to capture because NIR wavelengths provide deep tissue information. Figure 3 shows
the measured relative spectral response of the prototype camera.

710nm

850nm

970nm

560nm

590nm

620nm

490nm

520nm

470nm

(a)
(b)
Fig. 2. (a) Multi-spectral compound eye camera (without filters) and (b) wavelength assignment.
spectrum
10000

8000

Sensitivity (a.u.)

6000

4000

2000

0400

600

800

1000

Wavelength (nm)Fig. 3. Measured total spectral response of all 9 channels of the camera and the emulated spectral
measurements from burn tissue response (derived from SFDS measurements in the previous
preclinical study)
System Integration: Though the micro-projector is a commercially available component, it is not
fully suited for this application and requires some modification. In terms of the hardware, thisprojector only uses Red, Green and Blue LEDs as its light source, however for this application; we
require illumination that spans both visible and near infrared regimes. This modification wassimply achieved by replacing the LEDs with a Quartz-Tungsten-Halogen bulb. This bulb isbattery powered, giving superior intensity stability and this modification also allows acquisition
speeds to be up to 3x faster as the LED approach would illuminate the tissue serially.
As this is a commercial mirco-projector, we do not have direct access to the onboard DMD. Here, thevideo projections do not display images linearly across the dynamic range of the DMD. Monitors
and projectors are tailored to the nonlinear response of human perception and hence convolve any
input image with a gamma function, before projecting it. In this case, if a purely sinusoidal
intensity image were to be used as an input to the projector, the intensity distribution projected on
to tissue would no longer be sinusoidal. We have characterized the intensity throughput function(gamma correction) for this specific projector by measuring the intensity of a series of grayscale
planar images reflected from a known reflectance standard (SRT-99-100, Labsphere, North SuttonNH) and used this to precondition every spatial frequency image used, ensuring that the resulting
intensity pattern projected onto tissue will represent a pure sinusoid.
The current systems development and integration is run off of a laptop as both camera andprojector are USB compatible. It can also be run off of a micro-board computer, such as a Beagle
Bone Black or Raspberry PI. By making this a self-contained unit, it would greatly enhance its
clinical utility by not requiring the unit to be tethered to a separate computer. This effort to makethe integrated device fully handheld and cable-free is in parallel development.
Burn Wound Tissue Simulating Phantom advancements for use in system testing and evaluation:
Based on our initial investigations of partial thickness burns, we have been developing a suite oftissue simulating phantoms that mimic burns and wound healing. While these phantoms can mimic
some optical properties encountered in burn wounds, there remain a number of limitations in theirfabrication methods and materials. These hinder full emulation across both visible and nearinfrared spectral regimes. Novel fabrication methods have now been developed to address theseissues, establishing a new phantom paradigm that can replicate burn wound severity in both visible
and near infrared regimes. These issues specifically address: 1) incorporation of stabilized
hemoglobin in hydrophobic media (PDMS) and 2) characterization of several scattering agents thatcan replicate sub- and extra-cellular changes both in effected and underlying burn tissue. This work
is currently in preparation for publication.

List of Publications Related to the Collaboration ResearchNone

List of Presentations ( Conference, Meeting, etc)
1. Keiichiro Kagawa, Izumi Nishidate, Rolf Saager, Norimichi Tsumura, Jun Tanida,“Measurement of absorption and scattering spectra with TOMBO-based multi-band spatial
frequency domain imaging: comparison with inverse Monte-Carlo simulation,” in Proc. Optics &Photonics Japan 2019, 2pF1 (Osaka University, Dec. 2-5, 2019).
List of Awards

Registration of research-theme continuation for next year
Prior consent from the collaboration partner in the Research Center is necessary.

YesNo

Research plan for the next year (from April 1, 2020 to March 31, 2021), if the collaboration research is continued.

Next year, we will quantify key biomarkers for rapid burn wound assessment and tissue response/recovery,such as: 1) burn depth, as well as, depth-specific 2) structural tissue damage, 3) hemoglobin (tissueviability) and 4) water (edema, inflammation) without perturbing tissue.
Validation using layered tissue-simulating media: Based on our initial investigations of partial thickness
burns, we have developed a suite of tissue simulating phantoms that mimic the differential sources of opticalcontrast, in depth, observed in burns and wound healing. These are multi-layer phantoms where we cancontrol the concentrations of hemoglobin and water absorption surrogates, as well as scattering spectra that

mimic structural changes in burns (e.g. collagen denaturation) and wound healing (tissue remodeling). We
have reported several recent developments and refinements in our methods to fabricate complex phantoms
that can replicate both scattering changes as well as functional changes observed from in vivo
measurements15-18. These new and advanced phantoms will provide better emulation of physiologic tissueproperties (in terms of both spectral response and tissue structure) and a quantitative, traceable proxy thatwill validate the performance and accuracy of proposed SFDS instrument in the context of graded burnseverities and wound healing, prior to its application in any preclinical study.
Outcomes: This step will establish the imager’s ability to determine burn depth and depth-specificphysiology a priori, ensuring future investigational deployment of this device (beyond the scope of thisapplication) will result in compelling preliminary data results while only utilizing a minimal in vivo
population size.
Quarter #1
Aim: Validation using tissue simulating
phantomsa) Phantom fabricationb) Dynamic (spectral) range testingc) Sensitivity to differentiation ofgraded burns

Quarter #2Quarter #3

Quarter #4