The Feasibility of Multispectral Optoacoustic Tomography in Different Diseases (FOMO)

The Feasibility of Multispectral Optoacoustic Tomography in Different Diseases: a Phase 1 Explorative Imaging Study (FOMO-study)

Optoacoustic imaging is a new and innovative imaging technique that combines the high contrast of optical imaging with the penetration depth and high spatial resolution of ultrasonography using the optoacoustic effect. It can resolve different endogenous tissue chromophores and may thereby provide insight in molecular changes associated with disease (-progression). It can be potentially used as an technique for diagnosis, treatment monitoring and disease localization. As the technique is relatively new in the clinical setting, there is not much clinical experience with optoacoustic imaging. The rationale for this study is to assess the technical feasibility of optoacoustic imaging in a variety of disease and to determine endogenous biomarkers for disease characterization for potential diagnosis and/or disease monitoring.

Study Overview

• Status: Completed
• Conditions: Sjogren Syndrome; Arterial Disease; Malignant Tumors
• Intervention / Treatment: Device: Multispectral optoacoustic tomography

Detailed Description

Optoacoustic imaging is a novel imaging method that is based on the optoacoustic effect, first described by Alexander Graham Bell in 1880. When biological tissue is illuminated with an ultrashort laser pulse, tissue chromophores absorb laser light and form pressure transient waves as a result of thermoelastic expansion. These optoacoustic or photoacoustic waves can be detected by wideband ultrasonic transducers around the tissue. Optoacoustic imaging is unique as it resolves optical contrast, but the resolution obeys the rules of ultrasonic diffraction; scattering of the ultrasonic signal in tissue is much weaker than for optical signals. Therefore, optoacoustic methods are insensitive to photon scattering within biological tissues and thereby provide higher spatial resolution with high sensitivity to tissue light absorption. In addition, it obtains penetration depths up to several centimeters, making it suitable for imaging deeper tissues within the body. Optoacoustic imaging has been shown to address clinically relevant aspects of various diseases, such as multiple prevalent cancers and inflammatory bowel disease.

Multiple imaging methods are based on optoacoustic imaging. However, unlike other types of optoacoustic imaging, multispectral optoacoustic tomography (MSOT) involves illumination of tissue with multiple wavelengths. Due to the high frequency pulse rate of the 9 laser, multiple wavelengths can be identified in one single image. Images can be processed using spectral unmixing algorithms in order to resolve different tissue chromophores, such as hemoglobin, deoxyhemoglobin, melanin and fat, which all have a distinct absorption spectrum or "spectral signature". This provides the ability to reconstruct an image by distinguishing and quantifying the contribution of specific absorbers including endogenous tissue chromophores.

Differences in the distribution of endogenous chromophores between normal tissue and diseased-tissue have been described extensively in preclinical and clinical optoacoustic studies. As the proliferation and metastatic spread in malignant tumors is highly dependent on angiogenesis, differences in hemoglobin concentration between normal tissue and tumor tissue is a well-known pathophysiological phenomenon Abnormal vascularization causing a local increase in hemoglobin concentration produces strong optoacoustic contrast, making optoacoustic imaging suitable for visualization of angiogenesis and tumors. This phenomenon could be used for diagnosis of a variety of malignant tumors, but potentially also for monitoring of disease progression after treatment. For example, relevant differences between hemoglobin distribution in benign and malignant thyroid tissue have been observed and the visualization of breast tumors using otoacoustics has been described.

For peripheral arterial disease, hemoglobin distribution and plaque characteristics are highly relevant biological features in the characterization of the disease. Nowadays, imaging modalities like X-ray CT are considered the gold standard, which give a relevant radiation burden to patients. Optoacoustic imaging has the potential for visualizing for example the peripheral arteries and the carotid artery, even in a 3D setting Identification of specific plaque characteristics like collagen and lipids would be a next step forward in visualization of plaque biology and its relationship with plaque rupture. This is topic of an already approved MSOT protocol in which 5 patients are enrolled.

As MSOT is experiencing a surge of interest in clinical investigation, there have been technological developments that enable imaging systems suitable for clinical use. The MSOT Acuity Echo (iThera Medical GmbH) that we use in the UMCG is dedicated for clinical research and similar to clinical ultra-sound technology in form and handling. Furthermore, it enables additional use of ultrasonography (OPUS) so that it delivers anatomical, functional and molecular information simultaneously. The MSOT Acuity Echo provides immediate feedback in the form of live images.

As multiple disciplines (surgery, radiology, nuclear medicine, oral and maxillofacial surgery, internal medicine) are interested in using the device, we aim to explore the possibilities of MSOT for various indications. We hypothesize that visualizing tissue chromophores with MSOT can lead to identification of molecular changes associated with disease (-progression).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with the following diseases will be included:

  1. Morbus Sjögren,
  2. A superficially located malignant tumor < 5 centimeter beneath the skin
  3. (Peripheral) arterial disease
• Age ≥ 18 years;

Exclusion Criteria:

• Patients with disease localizations or manifestations that do not enable good coupling between the optoacoustic probe and the skin, as decided by the researchers;
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Pregnant women. Women of childbearing potential need to undergo a pregnancy test before participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental MSOT measurement; imaged with the multispectral optoacoustic tomography device (MSOT Acuity Echo).	Device: Multispectral optoacoustic tomography; If patients are willing to participate in this study, they are imaged with the multispectral optoacoustic tomography device (MSOT Acuity Echo) at the department of nuclear medicine and molecular imaging. The imaging procedure takes 15 minutes at most.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optoacoustic Signal Analysis	Quantitative assessment of optoacoustic signals from tissue chormophores (e.g., hemoglobine, deoxyhemaglobine, water, lipid, and collagen). The signal of the different chormophores are described as arbitrary units (a.u.)	After informed consent the patient will be imaged for 15 minutes.
Comparison with Standard Imaging Modalities	Validation of optoacoustic imaging by comparing chromophore signals to imaging features from CT, MRI, PET, and/or ultrasound. Correlation coefficients or diagnostic accuracy metrics (e.g., sensitivity, specificity, area under the curve).	After informed consent the patient will be imaged for 15 minutes.
Histopathological Correlation	Correlation of optoacoustic findings with histopathological results from biopsy or surgical specimens. Agreement rate or correlation metrics (e.g. p-values)	After informed consent the patient will be imaged for 15 minutes.

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2020
• Primary Completion (Actual): October 14, 2021
• Study Completion (Actual): October 14, 2021

Study Registration Dates

• First Submitted: November 7, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Diagnostic; Non-invasive; Sjogren syndrome; Diagnose; Multispectral optoacoustic tomography; Optoacoustic imaging
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Sjogren's Syndrome
• Other Study ID Numbers: NL71894.042.19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Relevant research data on request
• IPD Sharing Time Frame: It will be available after the end date of the study. It will be available for 15 years after the study has ended
• IPD Sharing Access Criteria: PI and other researchers on request. They are able to access the Study Protocol and the Clinical Study Report
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No