Final Report Summary - HIFI (Hybrid Fluorescence Optoacoustic Imaging)
The general objective of the project is to produce a novel high performance Optical Imaging system and test its capabilities to diagnose rheumatic arthritis (RA), a highly prevalent disease, with the aim of reducing overall clinical costs. To do so, we focused on the Multispectral Optoacoustic Tomography (MSOT) technology, due to its unique capabilities (see section “state of the art before the project”) . While RA was chosen initially,ongoing research actions in the group of the scientist in charge showed that the RA is not well suited for assessment by optoacoustic technology. The problem is the presence of acoustic distorting objects (bone) in the anatomical areas where the illness is manifested. Therefore, at the beginning of the project, we switched the targeted disease to prevalent skin diseases.
State of the art before the project
Diagnosis of skin diseases is expensive since histology of biopsied samples is usually needed and the current imaging techniques can provide only a partial view of the dermis. The modern skin imaging portfolio today consists of optical imaging techniques (confocal microscopy and multiphoton microscopy)that have a short penetration depth due to light diffusion, allowing skin imaging of only a few hundred microns in depth. Conversely, acoustic imaging techniques have a good penetration depth covering the whole skin depth but the contrast mechanisms do not allow to visualize crucial parameters like blood oxygenation or the concentration of biologically relevant optically absorbing species like melanin.
In contrast, the use of the above mentioned optoacoustic technology provides images with good optical contrast and the depth to resolution ratio of acoustic systems. Consequently, in theory, optoacoustic technologies could image optical absorbing objects raging from tens of microns to hundreds of microns size through the whole depth of the skin (1-4mm).
Therefore, we predicted that due to its unique depth imaging capabilities, MSOT can highly impact the dermatology clinical routine.
Development of the project
Phase 1.
In the first phase of the project, we assessed the right parameters of the optoacoustic technology needed to address the skin imaging problem. We analyzed and determined the right frequency of the optoacoustic detector needed to image the different layers of skin with special attention to the frequencies required for imaging the microvascular tree. We explored various illumination schemes capable of providing homogeneous illumination patterns that would lead to higher quality images and better tomographic formulations. We also proposed different equalization schemes for the optoacoustic signals, in order to resolve different structures of the skin. Once the right parameters were found we miniaturized the technology in order to make it suitable for imaging in the clinics. Further research was done towards the multispectral acquisition scheme needed to achieve functional and molecular imaging of the skin. An optimized multispectral scheme would have the ability to resolve blood oxygenation, melanin concentration and other medically relevant optical absorbers.
Once all the parameters were optimized we implemented the method in a handheld fast imaging system suitable for the clinic.
Phase 2.
In the second phase of the project we tested the system in the clinical setting in order to image several different skin conditions.
One of them was psoriasis, a highly prevalent disease that greatly affects the quality of life of the patients suffering from it. Our system showed great capabilities for imaging the disease, revealing for the first time aspects of it that were previously obscured. More specifically, we have been able to image the vascular bed with unprecedent resolution to depth ratio, being able to image the capillaries up to 1.4 mm depth. A new set of objective biomarkers for psoriasis was proposed, replacing former subjective disease diagnosing and follow up indices based on visual examination. We have been also able to image the melanin dynamics as reaction to exposure to UV radiation. In addition, we have been able to image bening moles, with unprecedented resolution to depth ratios.
State of the art after the project
With the skin imaging prototype provided as a result of this project, a novel asset with greatly improved imaging capabilities for dermatology has been released. The new system is able to perform anatomical, functional and molecular optical imaging with unprecedented resolution to depth ratio. The new technology is already changing our view of an important disease like psoriasis by revealing for the first time its dermal vasculature structure. Initial clinical trials with other conditions (eczema, vasculitis, angioma and others ) suggest that the system has a tremendous potential to impact the clinics in the short to medium term. We are convinced that the imaging capabilities achieved by optoacoustic technologies will lead to better diagnosis, improved treatment strategies and thus result in an overall reduction of the costs in dermatological healthcare.
Training activities.
The researcher has gone through a complete set of training activities.
Such activites can be divided in two groups.
Group 1). Training activities orientated to master the technical development of MSOT.
The researcher has built a novel MSOT imaging system from all perspectives. He has tested it with phantoms and in a clinical setting. Such activities have allowed the researcher to become an expert in all the areas realted to MSOT technological development including: instrumentation (transducer, amplifiers, transaltion stages, DAQs, laser sources), optoacoustic signal processing, MSOT tomographic reconstruction, MSOT image representation, MSOT mechanical desing, testing, and clinical implementation.
As a result, the researcher has become a recognized expert in the design and development of MSOT technology.
Group 2). General training activities orientated to allow the beneficiary of the scholarship become an independent researcher.
The researcher had the change to acquire several skills which are required to become a independent researcher. Those abilities include: supervision of phD students, presentation skills and patent writing.
Furthermore, the researcher has acquired a general view on the technology transfer process, a general view of the state of the art in general biomedical optical imaging with a specific view in MSOT, and greatly increased his scientific contact network.
The mentioned skills were acquired by doing the following activities:
-Mentoring and guiding a phD student.
-Attendace to international congresses, giving oral presentations on them.
-Attendance to summer schools.
-Attendance to weekly seminars, giving oral presentation on them.
-Participation in the development of a patent
At the end of the project the researcher was a appointed as a junior group leader at the host institution, making a decisive step towards becoming an independent researcher.
State of the art before the project
Diagnosis of skin diseases is expensive since histology of biopsied samples is usually needed and the current imaging techniques can provide only a partial view of the dermis. The modern skin imaging portfolio today consists of optical imaging techniques (confocal microscopy and multiphoton microscopy)that have a short penetration depth due to light diffusion, allowing skin imaging of only a few hundred microns in depth. Conversely, acoustic imaging techniques have a good penetration depth covering the whole skin depth but the contrast mechanisms do not allow to visualize crucial parameters like blood oxygenation or the concentration of biologically relevant optically absorbing species like melanin.
In contrast, the use of the above mentioned optoacoustic technology provides images with good optical contrast and the depth to resolution ratio of acoustic systems. Consequently, in theory, optoacoustic technologies could image optical absorbing objects raging from tens of microns to hundreds of microns size through the whole depth of the skin (1-4mm).
Therefore, we predicted that due to its unique depth imaging capabilities, MSOT can highly impact the dermatology clinical routine.
Development of the project
Phase 1.
In the first phase of the project, we assessed the right parameters of the optoacoustic technology needed to address the skin imaging problem. We analyzed and determined the right frequency of the optoacoustic detector needed to image the different layers of skin with special attention to the frequencies required for imaging the microvascular tree. We explored various illumination schemes capable of providing homogeneous illumination patterns that would lead to higher quality images and better tomographic formulations. We also proposed different equalization schemes for the optoacoustic signals, in order to resolve different structures of the skin. Once the right parameters were found we miniaturized the technology in order to make it suitable for imaging in the clinics. Further research was done towards the multispectral acquisition scheme needed to achieve functional and molecular imaging of the skin. An optimized multispectral scheme would have the ability to resolve blood oxygenation, melanin concentration and other medically relevant optical absorbers.
Once all the parameters were optimized we implemented the method in a handheld fast imaging system suitable for the clinic.
Phase 2.
In the second phase of the project we tested the system in the clinical setting in order to image several different skin conditions.
One of them was psoriasis, a highly prevalent disease that greatly affects the quality of life of the patients suffering from it. Our system showed great capabilities for imaging the disease, revealing for the first time aspects of it that were previously obscured. More specifically, we have been able to image the vascular bed with unprecedent resolution to depth ratio, being able to image the capillaries up to 1.4 mm depth. A new set of objective biomarkers for psoriasis was proposed, replacing former subjective disease diagnosing and follow up indices based on visual examination. We have been also able to image the melanin dynamics as reaction to exposure to UV radiation. In addition, we have been able to image bening moles, with unprecedented resolution to depth ratios.
State of the art after the project
With the skin imaging prototype provided as a result of this project, a novel asset with greatly improved imaging capabilities for dermatology has been released. The new system is able to perform anatomical, functional and molecular optical imaging with unprecedented resolution to depth ratio. The new technology is already changing our view of an important disease like psoriasis by revealing for the first time its dermal vasculature structure. Initial clinical trials with other conditions (eczema, vasculitis, angioma and others ) suggest that the system has a tremendous potential to impact the clinics in the short to medium term. We are convinced that the imaging capabilities achieved by optoacoustic technologies will lead to better diagnosis, improved treatment strategies and thus result in an overall reduction of the costs in dermatological healthcare.
Training activities.
The researcher has gone through a complete set of training activities.
Such activites can be divided in two groups.
Group 1). Training activities orientated to master the technical development of MSOT.
The researcher has built a novel MSOT imaging system from all perspectives. He has tested it with phantoms and in a clinical setting. Such activities have allowed the researcher to become an expert in all the areas realted to MSOT technological development including: instrumentation (transducer, amplifiers, transaltion stages, DAQs, laser sources), optoacoustic signal processing, MSOT tomographic reconstruction, MSOT image representation, MSOT mechanical desing, testing, and clinical implementation.
As a result, the researcher has become a recognized expert in the design and development of MSOT technology.
Group 2). General training activities orientated to allow the beneficiary of the scholarship become an independent researcher.
The researcher had the change to acquire several skills which are required to become a independent researcher. Those abilities include: supervision of phD students, presentation skills and patent writing.
Furthermore, the researcher has acquired a general view on the technology transfer process, a general view of the state of the art in general biomedical optical imaging with a specific view in MSOT, and greatly increased his scientific contact network.
The mentioned skills were acquired by doing the following activities:
-Mentoring and guiding a phD student.
-Attendace to international congresses, giving oral presentations on them.
-Attendance to summer schools.
-Attendance to weekly seminars, giving oral presentation on them.
-Participation in the development of a patent
At the end of the project the researcher was a appointed as a junior group leader at the host institution, making a decisive step towards becoming an independent researcher.