“An extensive perspective on biomedical microwave engineering: the Galway experience”

Dr. Giuseppe RuvioBioInnovate Fellow

School of Engineering and InformaticsNational University of Ireland, Galway

Presentation Overview

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• Biomedical engineering research at NUIG• Breast cancer microwave imaging• Bone microwave imaging• Microwave interventional treatments

Biomedical engineering research at NUIG

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Physician driven

Long/medium-term academic

projects

Timely technology transfer

opportunities

International collaborations

Presentation Overview

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• Biomedical research at NUIG• Breast cancer microwave imaging�Motivation�Tissue characterisation�Antennas as sources and sensors�Radar principles�Pre-clinical system assessment

• Multi-modality tissue-mimicking phantoms• Microwave bone imaging• Microwave interventional treatments

Why Breast Cancer Microwave Imaging?

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Advantages of Radio-frequency based methods:• Higher contrast compared to radiographic density exploited by X-ray mammography• Non-ionizing and very low-power radiation• No breast compression during the exam• Reduced risks of faulty diagnosis• More efficient health system budgets• Reduced machinery costs and broader sustainable early detection campaigns

Limitations of conventional breast screening:• Up to 34% of all breast cancers missed by conventional mammography • Nearly 70% of all breast lesions identified by mammography are benign• Low-dose ionizing radiation• Breast compression during the exam• Traumatic experience for misdiagnosis• Costs for the health system• Unaffordable wide screening campaigns and early detection

Microwave Imaging

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Optical visionLight reaches the eyes. Its message is sent to brain which “forms” the image.

Microwave imagingThe detection scene is sensed by microwave. Likewise in optical vision, antennas play the role of eyes. But for reciprocity, they can be the source and the sensor at the same time!Why microwaves?Penetration of non metallic optically opaque materialsSensitive to the dielectric and conductivity contrastLow-cost engineering

What are microwaves?

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Microwave frequency bands:Letter Designation Frequency range

L band 1 to 2 GHzS band 2 to 4 GHzC band 4 to 8 GHzX band 8 to 12 GHzKu band 12 to 18 GHzK band 18 to 26.5 GHzKa band 26.5 to 40 GHzQ band 30 to 50 GHzU band 40 to 60 GHzV band 50 to 75 GHzE band 60 to 90 GHzW band 75 to 110 GHzF band 90 to 140 GHzD band 110 to 170 GHz

IEEE

RADAR

BANDS

Microwaves are electromagnetic waves with frequency ranging from hundred of MHz (300?) to hundred of GHz(300?). Wavelength can varies from meters to millimeters.

Radar principle

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The target scatters the incoming electromagnetic signal. The radar antenna receives the scattered copy of the launched signal. From phase and amplitude, the radar can extract information regarding location and shape of the target.

Microwave Imaging

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Tx Rx

Scatterer

Air/skin interface

Hidden scatterer

Obscuring obstacle

Incident field↓

known

Scattered field↓

measured

“Seeing” through microwaves: DetectLocalise

Characterise

Increasing difficulty

Let us define all the elements of the problem

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• Mathematical model• Antenna• Media• Image formation algorithm

Mathematical model – Maxwell’s equations

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E = electric fieldH = magnetic fieldε = permittivity, the measure of the

resistance that is encountered when forming an electric field in a medium

µ = permeability, the degree of magnetization of a material in response to a magnetic field

ρv = charge density is a measure of electric charge per unit volume of space, in one, two or three dimensions

σ = conductivity, a measure of a material's ability to conduct an electric current

A macro and convenient description of the matter for electromagnetic problems!

Definition of antenna

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IEEE Standard Definition: a usually metallic device for radiating or receiving radio waves.

Source Transmission Line Antenna Free-Space

Standing Wave Radiated free-space wave

• receive/transmit energy• enhances energy radiation in some directions and suppresses it in other ones.• optimise energy transfer

RF/Microwave interaction with biological tissues

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At RF/Microwaves the quantum energies are well below the ionisation potential of any known substance. This type of radiation cannot physically alter the atoms and change them into charged particles called ions.

Excitation of coherent vibrational and rotational modes requires considerably less energy than ionisation and it can occur at RF.

Many other possible biological effects require energies well below the level potentials, such as heating, dielectrophoresis, depolarisation of cell membranes, and piezoelectric transduction.

Permittivity

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� = ���� Relative permittivity of the material

Permittivity of the vacuum

�� = ��� − �����In order to take into account the dipolar polarisation, �� is expressed by:

where��� =

��� − ���1 + ���� + ��� ���� =

��� − ��� ��1 + ����

��� and ��� are the values of the real part of the relative permittivity at frequencies zero and infinity, respectively; � is the relaxation time which is the time for the dipolar polarisation to reach saturation.Dipolar polarisation is dominant in the case of water or in tissues with high water content.

Detection algorithm

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Acquisition data Clutter rejection

Beamforming like, Migration, Time Reversal, MUSIC like

Breast cancer microwave imaging

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• Complex heterogeneous scenario• Changing from patient to patient (i.e. from mostly fatty to very dense breasts)• Near-field imaging• Critical a priori antenna characterisation• Non-uniform antenna-skin distance

Common image formation proceduresBeamforming

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Technique burrowed from Ultrasound imaging

Common image formation proceduresHolography

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Holography approaches exhibit a higher signal to noise ratio (SNR), increased focus quality

Common image formation proceduresInterferometric-MUSIC

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MUltiple SIgnal Classification (MUSIC) is an algorithm used for frequency estimation and emitter location.

In many practical signal processing problems, the objective is to estimate from measurements a set of constant parameters upon which the received signals depend.

In breast cancer detection applications, MUSIC algorithms can be used to detect the dielectric contrast between benign and malignant tissues.

Pseudospectrum I-Music

( )( )[ ]∏

=

−=

fN

ii

ki

kMUSICI

fAP

r

1

2

1φ

Interferometric strategy

Comparing beamforming and holographyThe importance of analytical modelling

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Motivation: BF and HI are analytically compared against a homogeneous scattering scenario which is pertinent to breast imaging.

An accurate analysis of each algorithm was carried out in terms of critical parameters suchas the operating frequency range, the number of scatterers and data discretization. This formal analytical approach enables a rigorous performance comparison of these techniques, which has not been previously reported.

Only a vague qualitative comparison can be extrapolated from the literature, where highly-cited contributions present the performance of these procedures on the basis of significantly different datasets and experimental configurations.

Comparing beamforming and holographyThe importance of analytical modelling

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Conclusion:• As long as criterion � ≥ 4����� is fulfilled, discrete

data will produce reconstructions in the same way as if no sampling occurred

• Nearly three times less samples are required to avoid aliasing using BF compared to HI under the same conditions.

• Frequency bandwidth can greatly help in reducing artefacts

HI BF

22m

17m

8mR. Solimene, A. Cuccaro, G. Ruvio, D. Flores Tapia, and M. O’Halloran, “Beamforming and holography image formation methods: an analytic study”, Optics Express Vol. 24, Issue 8, pp. 9077-9093 (2016)

From simplified scenarios…

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Benchmarking the imaging algorithm with ideal sources

• The detection of a single inhomogeneity is performed on the basis of the scattered field which is collected over 12 different positions taken uniformly (360/12)° around the phantom.

• The algorithm is first evaluated in the presence of an inhomogeneity placed inside the breast tissue just below the skin tissue at the coordinates (40 mm, 20 mm) referred to the centre of the coaxial structure.

• This configuration takes into account the least favorable scenario for detection as very few scans contribute to reconstruction of the target.

• The phantom has been scanned by an ideal infinite dipole and an FDTD based numerical tool is used to solve the forward scattering problem.

• The tumor detection is accurate.

… to a more realistic problem description

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2.5D problem – Round interface – Multi-monostatic case

• The cancer detection problem is treated by considering a coaxial cylindrical structure with a diameter 2rs = 100 mm which simulates the skin and breast tissue layers.

• The scattered field data are collected under a multimonostaticconfiguration (i.e. TX and RX are co-located) over a circle of radius rs = 50 mm in correspondence to N measurement positions (ro1, ro2,…,roN).

… to a more realistic problem description

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Presence of two tumours• These two locations represent different challenges for the detection system. On one

side we have the tumour T1 that scatters a stronger attenuated signal compared to T2. But considering the multi-monostatic radar configuration of the system, for the detection of the more superficial tumour T2, the algorithm obtains the most significant contribution from a limited number of scanning positions.

• The reconstruction is correct and the two tumours sufficiently well localised.

… to a more realistic problem description

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2.5D MRI-based numerical phantom

Small tumour (5-mm diameter) inserted in MRI-based numerical model

… to a more realistic problem description

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3D MRI-based numerical phantomImporting/creating voxel models from digitized MRI scans:

• Voxel size control • 3-D rotation of the numerical phantom• Customizable dispersion model for each

tissue

… to a more realistic problem description

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Experimental results• Measured data were collected in the frequency

domain across N=36 scanning positions uniformlydistributed around the phantom.

• Range [1-3] GHz.• Multi-monostatic configuration.• The system antenna + phantom was immersed

into a coupling medium which presentsequivalent properties to the adipose tissue.

Schematic of the measurement setup

Antennas Geometry

Semifolded MonopoleAntipodal Vivaldi antenna

Planar Monopole

… to a more realistic problem description

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Experimental resultsThe phantom has an overall diameter of 114 mm including the 2 mmthick skin. The fibroconnective and fibroglandular regions have 68 mmand 20 mm diameters, respectively.

… to a more realistic problem description

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Experimental results

… to a more realistic problem description

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3D skin shape reconstructionBreast Microwave Imaging techniques require information on the skin shape in order to improve their performance. This information is useful:• as reference system to locate the detected lesion• to declutter effectively the measured data• to give a zero-th starting estimation in iterative inverse problems• to improve the penetration of the signal

Study on MRI-derived breast model from the Wisconsin repository.The phantom is immersed in the coupling liquid with εr = 10).A pulse with a band from 0 to 4 GHz is generated as excitation

… to a more realistic problem description

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3D skin shape reconstructionValidation on 2D section

Reconstruction with ideal sources (plane wave)

Reconstruction with real Vivaldi antenna

Scattered signal with phantom at 10-mm distance

Scattered signal without phantom

Signal component due to phantom

… to a more realistic problem description

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3D skin shape reconstructionAntenna located in 104 positions laying on a hemispherical surface around the breast

By subtracting the antenna response in its standaloneconfiguration from the signal in presence of the breast, thesignal due to the presence of the skin only is obtained.

The distance betweenantenna and skin can be estimated from thetotal time that pulse takes to come back to theantenna port.

… to a more realistic problem description

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3D skin shape reconstructionComparison between real skin shape (left column) and estimated (right column) in the 3D case with numeric realistic phantom

Estimation error increases for points with reduced skin-antenna distance and/or with rapid convexity variation

Preliminary results are very promising but further improvement can be achieved by increasing the number of measurement points

Towards a microwave scanning system where the same antennas are used to reconstruct skin profile and spot lesions!

Presentation Overview

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• Biomedical research at NUIG• Breast cancer microwave imaging• Multi-modality tissue-mimicking phantoms• Microwave bone imaging• Microwave interventional treatments

Oil-in-gelatine 2-D breast phantom

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• Breast phantoms based on oil-in-gelatin emulsions can reproduce the electric properties of various normal and malignantbreast tissues.

• Stable mechanical and electromagnetic properties are achievable by properly mixing the 50% kerosene - 50% safflower oilsolution with a formaldehyde-based emulsion.

• Due to their gelatinous consistence, these materials are significantly convenient for easy and inexpensivemanufacturability.

• An essential property of these materials is the capability to create heterogeneous and anthropomorphic structures withlong-term stability.

Emulsion preparation Dielectric properties measurement

MRI-scanningMRI cross-section

Mixed-technology 3-D breast phantom

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• Complex phantom moulds: External skin, Internal skin and Fibroglandular

• Preparation of materials to mimic breast tissues. High precision ingredient scaling and controlled heating and stirring

Presentation Overview

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• Biomedical research at NUIG• Breast cancer microwave imaging• Multi-modality tissue-mimicking phantoms• Microwave bone imaging• Ablation of vessels or lesions in the gastrointestinal tract

3D-Microwave Scanner

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The 3-D scanner here presented is meant to extend the investigation which was carried out in previous slides in a more controlledenvironment

Functional blocksof the scanner

The prototype is made of the following parts:

• Two printed antipodal Vivaldi antennas that can be maneuvered to adjust their height and distance from thephantom;

• A turntable that rotates the phantom with an accuracy of ± 1°;

• An acquisition unit to synchronize the antenna/phantom positioning with the data acquisition;

• A VNA to measure the S-parameters at the antennas' terminals;

Measurement & Numerical setup

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• For a fixed height, measured data were collected inthe frequency domain across N=36 scanning positionsuniformly distributed around the phantom.

• The system records S11 and S22 (multi-monostaticconfiguration) of the antennas sampled across 801equally sparse points in the frequency range [0.5-4]GHz.

• The system antenna + phantom was immersed into acoupling medium obtained with a mixture of a 50%kerosene-50% safflower oil solution and de-ionisedwater in the proportion of 80% and 20%

Measurement & Numerical setup: Testing

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Muscle

The scanner was preliminary assessed for a very simple homogeneous scenario with the investigation scene totallyfilled with the coupling medium and an 8-mm thick cylindrical metal bar used as target.

Measurement & Numerical setup : Realistic phantom

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Tissues Conductivity [S/m]

Relative permittivity

εrBone cortical 0.45 11.20

Marrow 0.11 5.26Muscle 1.95 52.26Fat 0.12 5.25

Skin 1.78 42.44

A realistic phantom that mimics a cow's leg was prepared by using a bovine metacarpal bone section with muscletissue attached and wrapped into pork fat and turkey skin for easier handiness. The phantom has an overall diameterof approximately 100mm and the length of 250mm with the bone-section of an approximate diameter of 28 mm.Three slices spaced 10mm were considered for the screening with 36 scans per each slice.

Dielectric properties of corresponding human tissues in phantom at 2.75 GHz.Phantom immersed into a coupling medium

Image reconstruction of realistic phantom

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-0.06-0.04

-0.020

0.020.04

0.06

-0.06-0.04

-0.020

0.020.04

0.060

0.010.02

x [m]y [m]

z [m

]

Sagittal x-ray scan of the phantomCross-section sketch of the phantom

3-D image reconstruction of the tibia and fibula in the phantom

Presentation Overview

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• Biomedical research at NUIG• Breast cancer microwave imaging• Multi-modality tissue-mimicking phantoms• Microwave bone imaging• Microwave interventional treatments

Gastroesophageal Varices

Gastroesophageal Varices

Acute bleed: 20-30% mortality

Banding

The OpportunityPROBLEM

- 2-4 interventions

- Average treatment takes 50 days

- Bleeds in varices awaiting treatment

- Rebleeding at ulcers caused by banding

- Varices reoccur in 75% of patients 2 years after banding

MARKET

Market

- 200,000 banding procedures annually in the US

- 600,000 patients with varices in US and Europe

- Ablation reimbursement = 1900 USD (CPT 43229)

Concept

Why MWs?- Direct heating- Speed- Penetrates through tissue- Effective at heat sinks- Sparing of surface tissue- Not affected by tissue heterogeneity- Endoscopic delivery

RFMicrowaves

Ultrasound

DC

Laser Cyro

High Level Project Overview

Design Optimisation / Dosing / further in vivo testing

Dec ‘15 May ’16(end of Stage 1)

Proof of principle in vivo study

Benchtop prototype testing

MW Applicator Development◦ Can we ablate tissue using MWs?

◦ Time / power required◦ Optimum frequency◦ Suitable antenna for use with endoscope cap

◦ Can we ablate while preserving the mucosa?◦ Can this system be used to treat varices?

◦ Coagulate blood◦ Collapse vessel

Bench testing at KS with MW antenna

Applicator Design

Coaxial cable

Antenna configuration

Cooling

Deflector hood

Ablation

Cap

Cooling

Scope

Antenna

MW

Multiphysics Analysis

Test cap

Antenna

Plan view showing ablation zone

44 deg C contour

60 deg C contour

Benchtop Testing

Bench testing arrangement

Antenna

Test capTest specimen

Results of Tissue Ablation

Ablated tissue

Spared mucosal tissue

Cap applicator

(10 seconds, 85 W power, 2.45 GHz Frequency)

In Vivo Testing

Mesenteric vein

Main Aim/Outcome- Determine if MicroWave (MW) energy can be used to stop

blood flow through a blood vessel with similar characteristics to oesophageal varices

Secondary Aims / Outcomes- Can MW ablation be used to stop blood flow while sparing

mucosal layer- Investigate operational window- Analyse risk that treatment causes mobile thrombi

Porcine splenic vein

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Ablation process

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MW probe

Results

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Ablation within 10 sec

Equine model

Ablation using cap

Vacuum

Cap

Antenna

Results

Ablation zone

Treatment criticalities

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Physician driven technology requires:• Real-time monitoring of the

treated zone• Evidence of occurred treatment• Minimised treatment duration• Minimum required control

functions

Haemostasis (CREO Medical)RF energy for cutting or desiccating issue structures and high frequency microwave energy for coagulating or ablating tissue an antenna structure that can deliver

RF energy for cutting and microwave energy for controllably coagulating small blood vessels, a deployable needle to introduce a viscous fluid in the region between the mucosal and sub-mucosal layer of the colon to raise a sessile lesion from the surface to allow it to be dissected, and a ‘speedboat’ shaped hull underneath the antenna to prevent the structure being pushed through the bowel wall

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Antenna design (omni-directional)

Monopole antenna

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• “Spherical” heat zone

• Preventing back heat propagation on the feeding cable (tear-drop effect) by using a choke

• Miniaturisation (minimum diameter)• Mechanical robustness• Restricted to medical grade materials and

assembly

◦ To direct heat flow ONLY on targeted tissues

◦ To spare healthy tissues

◦ To adapt in very heterogeneous scenarios

◦ To enable physicians to tailor treatment plans

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Antenna design (directional applicator)

Antenna challenges

• Stable impedance matching• Resilient to different working conditions

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Antenna challenges

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• Directive heat flow• Sparing non targeted healthy tissues• Preventing back heat propagation on the feeding

cable (tear-drop effect)• Miniaturisation• Mechanical robustness• Restricted to medical grade materials and

assembly

Treatment criticalities

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Physician driven technology requires:• Real-time monitoring of the

treated zone• Evidence of occurred treatment• Minimised treatment duration• Minimum required control

functions

Animal Studies

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Proof of Principle Testing Acute Study Chronic

Study

Strictly related topics

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Microwave imaging Accurate dielectric properties measurement of biological

tissues

Controlled tissue-mimicking phantoms Microwave ablation

Main collaborators

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• Antenna & High Frequency Research Centre, Dublin Institute of Technology

• School of Physics, Dublin Institute of Technology• Second University of Naples, Italy• Sapienza University, Rome, Italy• ENEA Institute, Rome, Italy• Czech Academy of Science, Prague• Kansas State University• COST Action TD1301 “MiMed”• COST Action BM1309 “EMF-MED”

Thank you. Questions?

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