A prerequisite for successful chemotherapy is that the drugs reach its target, and that damage to healthy tissue is limited. However, when drugs are injected into the blood, less than 1% of the drugs accumulate in tumours. Microbubbles combined with focused ultrasound shows great promise in enhancing delivery of nanoparticles and drugs thereby improving cancer therapy. Focused ultrasound and nanoparticles can also be used to temporarily open the blood-brain barrier thereby allowing nanoparticles and drugs to enter into brain tissue, which enables treatment of brain disorders. At the Department of Physics, NTNU, we are using two types of new microbubbles to improve the delivery of nanoparticles and drugs in combination with focused ultrasound. Continue reading
Category Archives: NTNUmedicine
Bloggers: Anne Line Stensjøen, PhD Candidate, Department of Neuromedicine and Movement Science (INB), and Asta Håberg, Professor and Centre Director, Centre of Innovative Ultrasound Solutions (CIUS)
Glioblastomas are tumours that originate from brain tissue. It is both the most common and most aggressive type of brain tumour. The median survival at group level is only 10 months for glioblastoma patients in Norway, but it is difficult to predict how long an individual long patient will survive.
How fast brain tumours grow is important to know to make the best decisions with regard to treatment. Tumour growth can also tell us something about how aggressive the tumour is, and perhaps be used as a marker of prognosis. It has been difficult to assess tumour growth because it requires at least two magnetic resonance images (MRIs) of the brain before treatment is started. Continue reading
A revolt is being stirred up in the beamforming world, and CIUS is among the insurgents.
For the first time in history a beamforming challenge was organized in the field of Medical Ultrasonics.
“What is beamforming?”, I hear you say. Beamforming is what bats do. They send an ultrasound signal which gets reflected at targets in front of them, such as prey (insects, fruits) or obstacles (watch out for that tree!). The reflected signal comes back to the bat ears and then the bat knows where the targets are and how to move around. But how does the bat know that? That’s where beamforming comes into play. Beamforming is the process by which temporal data (what the bat hears) is converted into spatial maps (where things are in the world). The bat does it with specialized ears that filter sound differently depending on the direction: up sounds differently than down, left than right, close than far. The same trick is used by other animals. Dolphins use an acoustic lens to direct ultrasound in the forward direction, oilbirds use echolocation to navigate through tress and caves in complete darkness, blind people can learn to navigate around the world by clicking their tongues. All that’s beamforming. Continue reading
All ultrasound technologies in health care, maritime, and oil & gas make use ultrasonic transducers. For this reason, transducer design is a key research task of the Centre for Innovative Ultrasound Solutions (CIUS).
Ultrasonic transducers are devices that convert electrical signals into mechanical vibrations and vice versa at frequencies above the hearing limit of 20 kHz. This is comparable to loudspeakers and microphones in the audible frequency range. Ultrasonic transducers are also called ultrasound probes. So, in other words, the probes transmit and receive sound waves beyond the hearing limit
Different application areas require different types of probes in the frequency range from 20 kHz to approximately 10 MHz. The core of a probe conventionally consists of a layer of piezoelectric material, which is a material that deforms when an electric field is applied, and that can generate an electric signal when a mechanical pressure is applied. To increase the efficiency to transmit ultrasound waves into the transmission medium, e.g. water, gel, the human body, or an oil or gas pipeline, the probe needs to be matched acoustically to the propagation medium. This is typically done by applying acoustic matching layers, which are thin layers with well-defined thicknesses down to the micrometre range and with appropriate acoustic properties. Transducers can contain one to several thousand acoustic elements. All these elements need to be electrically connected to transmit and/or receive electronics. All these aspects make the design of ultrasonic transducers a multidisciplinary task that include physics, electronics, mechanics, and materials.
At the Department of Micro- and Nanosystem Technology, which is part of the Faculty of Technology and Maritime Science of the University College of Southeast Norway at Campus Vestfold in Horten, we are investigating different aspects of probes for applications in both medical, maritime, and industrial fields. Our ultrasound laboratory workshop allows the manufacturing of special custom-designed prototype ultrasound probes in the frequency range from approximately 1 to 10 MHz. These ultrasound probes can be either a single-element probe (one transducer element to transmit and receive the sound, see this Wiki article on Doppler fetal monitor) or an array probe consisting of multiple transducer elements that allows steering of the transmitted and received ultrasound beam.
One research topic that is under investigation as part of CIUS is the design and manufacturing of a dual frequency transducer for medical purposes. A dual frequency transducer can send and receive both lower and higher frequency sound. A potential application is the manipulation and detection of ultrasound contrast agents, which are tiny gas spheres that can be injected in the blood circulation for e.g. blood flow imaging. The dual frequency probe would allow for transmitting and receiving at different frequency ranges, but through the same probe surface. Such probe design could consist of several active piezoelectric layers, which can result in complex vibration modes and a more complex manufacturing procedure.
Another topic under investigation is self-heating of probes. In transmit, all electrical energy that is consumed but not transmitted into the transmission medium, is lost as heat within the probe itself. This leads to heating of the probe, and can even result in probe failure. The hypothesis is that theoretical investigation of the thermal principles behind this, and accurate modelling and measurements of temperature distributions within real ultrasonic probes, can lead to better understanding and methods in how to reduce heating problems that are currently experienced in some industrial applications.
Exploiting nonlinear distortion to switch from black and white to colour in underwater acoustic imaging
When ultrasound propagates through water nonlinear effects come into play and distort the signal originally transmitted (Figure 1). The effect of this distortion can be seen as a transfer of energy around what is called “harmonic frequencies”. For example if the signal originally transmitted has a frequency of 1 MHz, after nonlinear distortion it will show components around 1 MHz, but also 2 MHz, 3 MHz, etc. (Figure 1).
The component around 1MHz is called the fundamental and those around 2 MHz, 3 MHz, etc. are called second harmonic, third harmonic, etc. A “monochromatic” signal (we use this term from the optical field to qualify a pure tone with one single frequency) becomes “polychromatic”. One could say that nonlinear effects “add colours” to a signal. By “listening” around these harmonic frequencies additional information can be extracted.
In underwater acoustics however its applications seem to be reduced to the “parametric arrays”. These arrays usually quite large in size explore another effect nonlinearity that creates very directive sound at low frequency capable of penetrating deep into the ocean bottom. This type of sonars are most often used for “seeing beyond the ocean floor” also called sub-bottom profiling. There are today opportunities for using nonlinearity in applications such as seabed imaging or fish finding in ways similar to what is done in medicine with THI: second harmonic imaging in underwater acoustics.
It is surprising that Thomas Muir who first thought about using nonlinearity in underwater acoustics imaging did not limit himself to the second harmonic but went all the way to image targets using the fifth harmonic when we know that the sound level decreases by at least 6 dB per harmonic.
I had the chance to meet Tom Muir recently at a conference. I told him that we were trying to take his pioneering work further and mentioned his article on harmonic imaging to which he replied “this paper was quickly forgotten” but he was well aware that he tried harmonic imaging before it became widely spread in medical imaging.
Only six years ago when we first started some experiments to prove the feasibility of second harmonic imaging using echo-sounders (simple sonars for fish finding) we were limited by the technology. The bandwidth (frequency range) of the system did not allow receiving the second harmonic and separate systems needed to be used for transmit and receive. Today the systems bandwidth has exploded going from 70 to 140 kHz or even from 200 kHz to 400 kHz making second harmonic imaging easily available.
Using the second harmonic in addition to conventional imaging could not only improve the image quality but bring additional information about what we are imaging. Indeed when directing sound towards an object or an animal the level of sound reflected by it depends on the frequency of the incoming sound. Comparing the level of the sound received at the fundamental and second harmonic frequencies could help identifying targets.
Gathering information contained in the echo of the fundamental frequency and of the upper harmonics would be a bit like switching from black and white to colour television. Preliminary tests on more advanced sonars used for bottom mapping (multi-beam sonars) using the second harmonic seem to be very promising. So let us turn the colours on!
Two researchers at CEMIR, Atle Granlund and Richard Kandasamy have received the “Young Research Talents” – grants that is a part of the FRIPRO-funding (Norwegian link) for researchers early in their career. FRIPRO is an open, national competitive arena that covers all fields of research. It aims to promote scientific quality at the forefront of international research, boldness in scientific thinking and innovation, careers for young research talents and mobility for researchers early in their career. FRIPRO aims to contribute to strengthen Norway’s national knowledge base by funding broad-based, independent research, that is a prerequisite for all other research and is essential for future industrial development and for policymaking. Continue reading
This image won the prize for Best Scientific Image at the 8th International PhD Conference in Medical Imaging 2016:
Inspired by Vincent van Gogh’s signature bold, sweeping brush strokes, this contemporary piece evokes a meteor shower back-dropped by the majestic Milky Way stretching across the midnight sky.
It is a false-color image of a human breast cancer tissue section in which blood vessel walls and proliferating (growing/replicating) cells were labeled using immunohistochemistry. A digital image of the tissue section was acquired with a microscope. Then, a computer algorithm was used to segment the image into different classes or types of cellular and tissue components. Each color represents a different class (e.g., orange = blood vessel and yellow = proliferating cell).
The digital image of the human breast cancer tissue section was acquired at 40x with an Olympus VS120 slide scanner. K-means clustering was performed in MATLAB to segment the image into the different classes. This was part of a larger algorithm to automate the tedious task of counting proliferating blood vessels.
Blogger: Jane Atesoh Awuh, Postdoctoral Fellow, Department of Cancer Research and Molecular Medicine and Centre of Molecular Inflammation Research (SFF-CEMIR).
Most often we become passionate and involved in issues in this life for very personal reasons. I am particularly drawn to infectious diseases because I hail from a society that is plagued by one kind of infection or the other. If you are not killed by one infectious disease you will be by the other, and if not by disease, it will be by war or hunger. I know two relatives who died of tuberculosis, one of them only a couple of months ago. Tuberculosis (TB) is still a disease of poverty although there is increasing incidence even in developed countries. HIV and TB are a dangerous liaison wherein HIV infects and destroys the very cells that should protect us from TB. These diseases are still considered shameful and surrounded by stigma. Continue reading
Movember is around with a “trøndersk” spirit on Facebook, Instagram, and the city is filled with mustaches in different shapes and varieties. The goal is increased awareness of men’s health and prostate cancer – a disease we in the MR cancer group want to understand better.
How can cancer metabolism provide important information about prostate cancer?
Scientists around the world have shown that changes in metabolism are important characteristics of cancer. We have studied how metabolism is altered due to cancer and how metabolism is changed owing to cancer aggressiveness. Previously, we have found that the two molecules citrate and spermine may be markers for prostate cancer and also can reveal information about aggressiveness.
Prostate cancer is a heterogeneous type of cancer, and this is of importance for treatment and prognosis of patients. However, today there are no reliable methods for assessment of type of prostate cancer. Researchers world-wide are therefore searching for new methods that may provide diagnostic and/or prognostic information. Presence of the fusion gene TMPRSS2-ERG have been suggested to be a candidate method for risk stratification, and in a recently published study we investigated the link between prostate cancer metabolism and TMPRSS2-ERG.
The second CIUS full-day conference held on 23 November 2016 in Trondheim, attracted near 80 participants representing CIUS researchers, partners, collaborators and international speakers. The day had a varied programme and ample opportunity for networking across work packages, institutions, and fields of speciality.
CIUS director Asta Håberg opened the day before leaving the floor for the invited speakers Dr Alan Hunter from University of Bath, and Dr Hua Wang from MIT.
Dr Hunter spoke on the topic “Underwater crime scene investigation for the London Metropolitan Police”, where the challenge is to develop an autonomous, compact, easy-to-use and affordable sonar vessel for finding missing persons and objects related to crime. He took us through the progress in the project so far, and future challenges, like identifying small objects.
Dr Wang’s presentation on “Seismic Propagation in Borehole Environment” took us through the use of wave dispersion characteristics by modelling of single and dual cased wells. He presented a novel method for depicting and characterizing bore holes, even through double steel layers, using ultrasound.
After a quick update on plans for the CIUS website and intranet by web- and communications officer Kari Williamson, it was time for speed updates. The topics ranged from improving ultrasound technology and image analysis to clinical applications. See the programme below for details.
The partner presentations ranged from open heart surgery applications and innovative projects, to the use of portable ultrasound at the patient bedside, also by non-expert users.
First speaker was Erik Swensen, Vice President R&D at Medistim, who talked about the use and challenges of developing reusable ultrasound probes for monitoring vessel patency in open heart, peripheral and transplant surgery. He was followed by Svein-Erik Måsøy, CEO Inphase Solutions, who talked about innovation projects including using ultrasound for wireless transfer of information and power as well as for use in quality assurance. The last speaker in this section was Håvard Dalen, Professor NTNU and Senior Consultant Cardiology St. Olavs Hospital, who showed how portable ultrasound devices can be used with great success by medical students, medical residents and nurses, and how it improves diagnostic accuracy, and thereby reducing time to treatment
The final session saw updates from academia with Fabrice Prieur, Postdoc at UiO, talking about the use of 2nd harmonics, which is commonly used in medical ultrasound for SONAR imaging (non-linearity and its challenges). He demonstrated that the use of 2nd harmonics provides additional information also in SONAR. Lasse Løvstakken, Professor NTNU, taking us through the latest in Doppler, software beamforming, functional ultrasound imaging and 3D tracking. CIUS Board Director and Programme Manager at GE Healthcare, Eva Nilssen, concluded the conference with a summary of the day.
The next CIUS conference day will be held in the last week of April and by request from our partners, the CIUS spring meeting will be extended to 1.5 day to get more time for workshops and partner-academia interaction.
The presentations will be made available on the CIUS intranet.
- Opening and presentation of CIUS’ results for 2016 and plans for 2017 (Professor Asta Håberg)
- Underwater crime scene investigation for the London Metropolitan Police (Professor Alan Hunter, University of Bath, UK)
- Seismic Propagation in borehole environment (Dr. Hua Wang, MIT, USA)
- Presentation of CIUS intra- and internet pages (Kari Williamson, web- and communications, CIUS)
- Speed updates:
- Optimisation of Ultrasound Pulses for Second Harmonic Imaging, Thong Huynh, HSN
- Experimental Evaluation of Broadband Wave Propagation in Plates, Andreas Talberg, NTNU
- Deep learning, Erik Smistad, NTNU/SINTEF (Read Smistad’s blog on the same topic.)
- 3D Vector Flow, Morten Smedsrud Wigen, NTNU
- Improving Quality of Cardiac Ultrasound Images, Ali Fatemi, NTNU (Read Fatemi’s blog on the topic)
- Ultrasound and Multimodal Image-Guided Interventions, Tormod Selbekk, SINTEF
- VScan in Stroke Diagnosis and Follow-Up, Lars Mølgaard Saxhaug, NTNU/Levanger Community Hospital.
- The Dynamic Range of Adaptive Beamformers, Andreas Austeng, UiO
- Medistim (Erik Swensen, Vice President R&D)
- Inphase Solutions (Svein-Erik Måsøy, CEO)
- US cardiology in a non-expert setting (Nord-Trøndelag, HUNT) (Professor Håvard Dalen, St. Olavs Hospital and NTNU)
- Non linearity in underwater acoustics, and other things (Postdoc Fabrice Prieur, UiO)
- Ultrasound blood flow imaging – state of the art and future perspectives (Professor Lasse Løvstakken, NTNU)
- Closing remarks (Eva Nilssen, CIUS Board Director and Programme Manager GE Healthcare, and Asta Håberg, NTNU)