Hand-held Clinical Photoacoustic Imaging System for Real-time Non-invasive Small Animal Imaging

Summary

A clinical handheld photoacoustic imaging system will be demonstrated for real-time non-invasive small animal imaging.

Abstract

Translation of photoacoustic imaging into the clinic is a major challenge. Handheld real-time clinical photoacoustic imaging systems are very rare. Here, we report a combined photoacoustic and clinical ultrasound imaging system by integrating an ultrasound probe with light delivery for small animal imaging. We demonstrate this by showing sentinel lymph node imaging in small animals along with minimally invasive real-time needle guidance. A clinical ultrasound platform with access to raw channel data allows the integration of photoacoustic imaging leading to a handheld real-time clinical photoacoustic imaging system. Methylene blue was used for sentinel lymph node imaging at 675 nm wavelength. Additionally, needle guidance with dual modal ultrasound and photoacoustic imaging was shown using the imaging system. Depth imaging of up to 1.5 cm was demonstrated with a 10 Hz laser at a photoacoustic imaging frame rate of 5 frames per second.

Introduction

For the detection and staging of cancer, different imaging techniques are available. Some of the widely used imaging modalities are magnetic resonance imaging (MRI), X-Ray computed tomography (CT), X-Ray, ultrasound (US), positron emission tomography (PET), fluorescence imaging, etc.^1,2,3,4. But, some of the existing imaging techniques are either invasive, have harmful radiation, or are slow, expensive, bulky, or unfriendly to patients. Thus, there is a constant need to develop new, fast, and cost-effective imaging techniques for di....

Protocol

All animal experiments were performed according to the approved guidelines and regulations by the institutional Animal Care and Use committee of Nanyang Technological University, Singapore (Animal Protocol Number ARF-SBS/NIE-A0263).

1. Handheld Real-time Clinical PA and US Imaging System

1. The schematic of the handheld clinical PAI system³³ is shown in Figure 1a. It consists of a optical parametric oscillator (OPO) laser pumped by a frequency doubled nanosecond pulsed Nd:YAG pump laser, a bifurcated optical fiber bundle (Figure 1b), a custom-made 3....

Results

Figure 1: System description. (a) Schematic representation of the PAI system with dual modal clinical US system. OPO - optical parametric oscillator, OF - optical fiber bundle, FH - fiber holder, USM- clinical US machine. The fiber holder i.......

Discussion

Currently the cost of screening, diagnosis, and treatment of cancer is very high. There are different imaging modalities which are being used for cancer screening and diagnosis. However, a lot of these imaging techniques have limitations including bulky machine size, invasive diagnosis, unfriendliness to patients, too expensive, requirement of ionizing radiation, or use of radioactive contrast agents. Therefore, an efficient, cost effective, real-time imaging and guiding system is much needed. Combined US and PA imaging .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Q-switched Nd:YAG laser	Continuum	Surelite	Pump laser
Optical parametric oscillator	Continuum		OPO laser
Clinical ultrasound imaging system	Alpinion	E-CUBE 12R	Dual modal ultrasound and photoacoustic imaging system
Linear array ultrasound transducer	Alpinion	L3-12	128 element linear array transducer with centre frequency of 8.5 MHz, fractional bandwidth of 95%,
Bifurcated optical fiber	CeramOptec	Custom made	To couple the light from the laser to the handheld fiber holder
Lens	Thorlabs	LB1869	Focus light from the laser to the optical fiber
Ultrasound gel	Progress/parker acquasonic gel	PA-GEL-CLEA-5000	Acoustic coupling
Image Processing software	Mathworks	Matlab	Home made program using Matlab
Anesthetic Machine	medical plus pte ltd	Non-Rebreathing Anaesthesia machine with oxygen concentrator.	Supplies oxygen and isoflurane to animal
Pulse Oxymeter portable	Medtronic	PM10N with veterinary sensor	Monitors the pulse oxymetry of the animal
Animal distributor	In Vivos Pte Ltd, Singapore		Animal distributor that supplies small animals for research purpose.
Breathing mask	Custom made		Used along with animal holder to supply anesthesia mixture to the animal
chicken breast tissue	Pasar		Used to add depth to mimic human imaging scenario
23G needle	BD Precisionglide	23G,1 and half inch	Used for realtime needle guidance
Holder for the fiber optic cable	Custom made		To hold the input end of the bifurcated cable
Handheld probe	Custom made 3D printed		With two slots for the two output ends of the optical fiber and one slot for the ultrasound transducer
Methylene blue (10 mg/mL)	Sterop		Contrast agent for PA imaging
Laser tuning software	Surelite OPO PLUS	SLOPO	Software to tune the wavelength of OPO laser
Photodiode	Thorlabs	SP05/M	To detect the laser pulse to trigger the ultrasound system
Photodiode bias module	Thorlabs	PBM42	To amplify the photodiode signal to tigger ultrasound signal
Depilatory cream	Reckitt Benckiser	Veet	Used to remove hair from the imaging area
Laser power meter	Ophir	Starlite, p/n: 7Z01565	Used to measure the laser power