Idan Steinberg

A new method for tumor detection using induced acoustic waves from tagged magnetic nanoparticles

UNLABELLED Magnetoacoustic detection is a new method for the noninvasive, early detection of cancer. It uses specific superparamagnetic nanoparticles (NPs) that bind to tumor sites together with magnetic excitation and acoustic detection of the tumor-NPs complex. This work tests the feasibility of such method theoretically and experimentally. An extensive analytic model has been developed that shows an ability to detect small tumors, a few centimeters deep inside the tissue. A series of experiments were conducted to validate the theoretical model. The performance of specially designed solenoids was measured, and the detection of the tumor presence in phantom was demonstrated. Experimental results agree well with the theoretical calculations, providing preliminary proof of concept. We demonstrate the ability to detect a 5-mm diameter spherical tumor located 3 cm deep. Instrumentation and measurements are inexpensive and accurate. The accuracy, speed, and costs of this method show the potential for early detection of cancer. FROM THE CLINICAL EDITOR A sensitive and cost effective magentoacoustic tumor detection method is presented in this paper using superparamagnetic nanoparticles. The method is demonstrated in a phantom by detecting a 5-mm diameter spherical tumor located 3 cm deep.

Tumor localization using magnetic nanoparticle-induced acoustic signals.

Cancer is a major public health problem worldwide, especially in developed countries. Early detection of cancer can greatly increase both survival rates and quality of life for patients. A magnetoacoustic-based method had been previously proposed for early tumor detection, in a minimal invasive procedure, using magnetic nanoparticles (MNPs). This paper presents a supporting localization algorithm that can provide the clinician with essential tumor location data and could enable a sequential biopsy. It provides localization algorithm development, as well as its validation in both computerized simulations and in vitro experiments. Three-dimensional (3-D) tumor localization is demonstrated with an error of 2.14 mm and an overlapping volume of 84% of the actual tumor. The obtained results are promising and prove the feasibility of tumor localization using a time difference of arrival algorithm along with a magnetoacoustic detection scheme.

Multispectral photoacoustic method for the early detection and diagnosis of osteoporosis

Osteoporosis is a major health problem worldwide, with healthcare costs of billions of dollars annually. The risk of fracture depends on the bone mineral density (measured in clinical practice) as well as on the bone microstructure and functional status. Since pure ultrasonic methods can measure bone strength and spectroscopic optical methods can provide valuable functional information, a hybrid multispectral photoacoustic technique can be of great value. We have developed such a system based on a tunable Ti:Sapph laser at 750 - 950 nm, followed by an acousto-optic modulator to generate photoacoustic signals with frequencies of 0.5 - 2.5 MHz. Another system was based on two directly modulated 830nm laser diodes. The systems were used to photoacoustically excite the proximal end of a rat tibia. Spectrum analyzer with tracking generator was used for measuring both the amplitude and the phase at the distal end. Scanning along both the optical wavelength as well as the acoustic frequency enables full mapping of the bone transfer function. Analyzing this function along the wavelength axis allows deducing the gross biochemical composition related to the bone functional and pathological state. Analyzing the amplitude and phase along the acoustic frequency axis yields the speed of sound dispersion and the broadband ultrasonic attenuation - both have shown clinical relevance.

Multiplexing of fiber-optic ultrasound sensors via swept frequency interferometry

The use of fiber-optic sensors for ultrasound (US) detection has many advantages over conventional piezoelectric detectors. However, the issue of multiplexing remains a major challenge. Here, a novel approach for multiplexing fiber-optic based US sensors using swept frequency interferometry is introduced. Light from a coherent swept source propagates in an all-fiber interferometric network made of a reference arm and a parallel connection of N sensing arms. Each sensing arm comprises a short polyimide coated sensing section (~4cm), which is exposed to the US excitation, preceded by a delay of different length. When the instantaneous frequency of the laser is linearly swept, the receiver output contains N harmonic beat components which correspond to the various optical paths. Exposing the sensing sections to US excitation introduces phase modulation of the harmonic components. The US-induced signals can be separated in the frequency domain and be extracted from their carriers by common demodulation techniques. The method was demonstrated by multiplexing 4 sensing fibers and detecting microsecond US pulses which were generated by a 2.25MHz ultrasound transducer. The pulses were successfully measured by all sensing fibers without noticeable cross-talk.

Multilayer Mie Scattering Model for Investigation of Intracellular Structural Changes in the Nucleolus and Cytoplasm

Light scattering from biological cells has been used for many years as a diagnostic tool. Several simulation methods of the scattering process were developed in the last decades in order to understand and predict the scattering patterns. We developed an analytical model of a multilayer spherical scattering cell. Here, we describe the model and show that the results obtained within this simple method are similar to those obtained with far more complicated methods such as finite-difference time-domain (FDTD). The multilayer model is then used to study the effects of changes in the distribution of internal cell structures like mitochondria distribution or nucleus internal structures that exist in biological cells. Such changes are related with cancerous processes within the cell as well as other cell pathologies. Results show the ability to discriminate between different cell stages related to the mitochondria distributions and to internal structure of the nucleolus.

Emerging Intraoperative Imaging Modalities to Improve Surgical Precision

Intraoperative imaging (IOI) is performed to guide delineation and localization of regions of surgical interest. While oncological surgical planning predominantly utilizes x-ray computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US), intraoperative guidance mainly remains on surgeon interpretation and pathology for confirmation. Over the past decades however, intraoperative guidance has evolved significantly with the emergence of several novel imaging technologies, including fluorescence-, Raman, photoacoustic-, and radio-guided approaches. These modalities have demonstrated the potential to further optimize precision in surgical resection and improve clinical outcomes for patients. Not only can these technologies enhance our understanding of the disease, they can also yield large imaging datasets intraoperatively that can be analyzed by deep learning approaches for more rapid and accurate pathological diagnosis. Unfortunately, many of these novel technologies are still under preclinical or early clinical evaluation. Organizations like the Intra-Operative Imaging Study Group of the European Society for Molecular Imaging (ESMI) support interdisciplinary interactions with the aim to improve technical capabilities in the field, an approach that can succeed only if scientists, engineers, and physicians work closely together with industry and regulatory bodies to resolve roadblocks to clinical translation. In this review, we provide an overview of a variety of novel IOI technologies, discuss their challenges, and present future perspectives on the enormous potential of IOI for oncological surgical navigation.

A Reconstruction Method for the Estimation of Temperatures of Multiple Sources Applied for Nanoparticle-Mediated Hyperthermia

Solid malignant tumors are one of the leading causes of death worldwide. Many times complete removal is not possible and alternative methods such as focused hyperthermia are used. Precise control of the hyperthermia process is imperative for the successful application of such treatment. To that end, this research presents a fast method that enables the estimation of deep tissue heat distribution by capturing and processing the transient temperature at the boundary based on a bio-heat transfer model. The theoretical model is rigorously developed and thoroughly validated by a series of experiments. A 10-fold improvement is demonstrated in resolution and visibility on tissue mimicking phantoms. The inverse problem is demonstrated as well with a successful application of the model for imaging deep-tissue embedded heat sources. Thereby, allowing the physician then ability to dynamically evaluate the hyperthermia treatment efficiency in real time.

Quantitative study of optical and mechanical bone status using multispectral photoacoustics

Osteoporosis is a major public health problem worldwide. Here, we present a quantitative multispectral photoacoustic method for the evaluation of bone pathologies which has significant advantages over pure ultrasonic or pure optical methods as it provides both molecular information and bone mechanical status. This is enabled via a simultaneous measurement of the bones optical properties as well as the speed of sound and ultrasonic attenuation in the bone. To test the methods quantitative predictions, a combined ultrasonic and photoacoustic system was developed. Excitation was performed optically via a portable triple laser-diode system and acoustically via a single element transducer. Additional dual transducers were used for detecting the acoustic waves that were generated by the two modalities. Both temporal and spectral parameters were compared between different excitation wavelengths and measurement modalities. Short photoacoustic excitation wavelengths allowed sensing of the cortical layer while longer wavelengths produced results which were compatible with the quantitative ultrasound measurements.

Broadband ultrasonic sensor array via optical frequency domain reflectometry

We introduce a new approach for multiplexing fiber-based ultrasound sensors using Optical Frequency Domain Reflectometry (OFDR). In the present demonstration of the method, each sensor was a short section of Polyimide-coated single-mode fiber. One end of the sensing fiber was pigtailed to a mirror and the other end was connected, via a fiber optic delay line, to a 1X4 fiber coupler. The multiplexing was enabled by using a different delay to each sensor. Ultrasonic excitation was performed by a 1MHz transducer which transmitted 4μs tone-bursts above the sensor array. The ultrasound waves generated optical phase variations in the fibers which were detected using the OFDR method. The ultrasound field at the sensors was successfully reconstructed without any noticeable cross-talk.

Investigation of a dual modal method for bone pathologies using quantitative ultrasound and photoacoustics

Osteoporosis is a widespread disease that has a catastrophic impact on patients lives and overwhelming related healthcare costs. In recent works, we have developed a multi-spectral, frequency domain photoacoustic method for the evaluation of bone pathologies. This method has great advantages over pure ultrasonic or optical methods as it provides both molecular information from the bone absorption spectrum and bone mechanical status from the characteristics of the ultrasound propagation. These characteristics include both the Speed of Sound (SOS) and Broadband Ultrasonic Attenuation (BUA). To test the methods quantitative predictions, we have constructed a combined ultrasound and photoacoustic setup. Here, we experimentally present a dual modality system, and compares between the methods on bone samples in-vitro. The differences between the two modalities are shown to provide valuable insight into the bone structure and functional status.