SUper-Resolution Ultrasound Imaging of Erythrocytes (SURE) in Normal and Malignant Lymph Nodes

Study Overview
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Brief Summary
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The goal of this observational study is to visualize the small vessels in normal and cancerous lymph nodes on the neck with a new ultrasound technique. The main questions it aims to answer are: Is it possible to visualize the network of the smallest vessels in lymph nodes on the neck? Is it possible to distinguish between healthy and cancerous lymph nodes using different parameters? The participants will have 1-2 lymph nodes ultrasound scanned with a standard ultrasound technique and the new technique.

Detailed Description
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Super-resolution ultrasound using erythrocytes (SURE) is a new ultrasound technique for visualizing the very small blood vessels in the body. The technique uses tracking of the blood's red blood cells (erythrocytes) to achieve a higher resolution of the blood vessels' shape, structure, and blood flow. The technique makes it possible to create images with much higher resolution than normal ultrasound, which means that even very small blood vessels can be imaged and measured. In many diseases, the small blood vessels change their function or structure. One of the major disease groups where SURE has significant potential is cancer. In cancerous nodes, the small blood vessels change: they become twisted, irregular, and function poorly. If changes in the small vessels can be detected at an early stage using SURE, it can lead to quicker diagnoses and better evaluations of the effectiveness of treatment. In this study, the investigators aim to demonstrate the practical feasibility of SURE imaging in human lymph nodes and investigate the clinical relevance of SURE imaging in the diagnosis of malignant lymph nodes by comparing lymph nodes from healthy participants with lymph nodes from participants with head and neck cancer metastases or lymphoma.

Official Title
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SUper-Resolution Ultrasound Imaging of Erythrocytes (SURE) in Normal and Malignant Lymph Nodes

Conditions
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Head and Neck Cancer, Lymphoma, Lymph Node Metastasis

Intervention / Treatment
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* Other: Malignant lymph nodes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be 18 to 70 years of age, at the time of signing the informed consent Participants who can lie still for 1 minute Capable of giving signed informed consent Inclusion criteria for healthy participants: Participants who are overtly healthy as determined by medical history Participants who have a superficial lymph node laterally on the neck with a normal appearance on standard B-mode ultrasound available for SURE imaging Inclusion criteria for participants with head and neck cancer or lymphoma: Participants who, besides their untreated head and neck cancer or lymphoma, are overtly healthy as determined by medical evaluation and medical history Participants with untreated lymphoma or head and neck cancer and lymph node metastasis verified by a biopsy. Participants who have superficial lymph nodes laterally on the neck up to 2.5 cm (so the entire lymph node is in the SURE image) Participants who will have their lymph nodes surgically removed Exclusion Criteria: Pregnancy Dementia Physique making ultrasound scanning difficult Ongoing or recent (within the last 4 weeks) infectious disease (bacterial, viral, fungal, or protozoal) which may give rise to reactive lymph nodes Diseases that cause lymphadenopathy: Some chronic infectious diseases (HIV, Tuberculosis, Hepatitis B), Systemic diseases (rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, other rare systemic diseases*), Primary adrenal insufficiency (Addison´s disease), Leukemia, Lymphoma or other cancers (besides the type of cancer the participant is being examined for at the Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet) Drugs that cause lymphadenopathy: Antibiotics (Cephalosporins, Penicillin, Sulfonamides), Antiepileptics (Carbamazepine, Ethosuximide, Lamotrigine, Phenytoin, Primidone), Antihypertensives (Atenolol, Captopril, Hydralazine), Other (Allopurinol, Imatinib) Castleman's disease, Kikuchi's disease, Kawasaki disease, Inflammatory pseudotumor, Amyloidosis, Kimura disease, Rosai-Dorfman disease, IgG4-related disease, Still's disease, dermatomyositis, Churg-Strauss, histiocytosis, chronic granulomatous diseases, Autoimmune lymphoproliferative syndrome, lipid storage diseases.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Controls<br>Healthy participants | |
| Cases<br>Patients with malignant lymph nodes on the neck | Other: Malignant lymph nodes<br>* Patients with a condition; either lymphoma on the neck or head and neck cancer with lymph node metastases on the neck.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Super-resolution ultrasound image of normal and malignant human lymph nodes | With super-resolution ultrasound imaging, the investigators will visualize the microvasculature in the lymph nodes. | 1 minute | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vessel distribution | Visual distribution of the nodal microvasculature | 1 minute | 
| Microvessel density | The ratio of the vessel volume to the full volume in different regions | 1 minute | 
| Distance between vessels | The distance between vessels in different areas in microns | 1 minute | 
| Size of avascular areas | In mm2 | 1 minute | 
| Degree of tortuosity | Tortuosity index. The actual track path divided by the shortest linear distance from the start to the end of the track | 1 minute | 
| Volume flow | In mm3/s | 1 minute | 
| Flow velocity | In mm/s | 1 minute | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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head and neck cancer, lymphoma, lymph node metastasis, super-resolution ultrasound, microvasculature