Abstract
Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC), provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US) allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO) and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular) lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA) biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl). Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy.
Highlights
The most common route of dissemination for head and neck cancers is via the local lymphatic system, where patient prognosis relies heavily on the ability to detect cervical lymph node involvement [1,2,3]
Cervical ultrasound is a commonly utilized tool for non-invasive imaging of lymph nodes in the patient neck, where it is frequently combined with magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT) to determine patient staging in head and neck squamous cell carcinoma (HNSCC) and other diseases
The transducer was first focused on the thyroid gland, where it is well-defined as a hyperechoic solid structure when imaged by gray scale sonography (Figure 1B and C) [35,36,37,38]
Summary
The most common route of dissemination for head and neck cancers is via the local lymphatic system, where patient prognosis relies heavily on the ability to detect cervical lymph node involvement [1,2,3]. HF US is a noninvasive, real-time technique that allows imaging of internal structures down to 30 microns using gray scale or brightness (B)-mode [9]. This resolution allows for real-time monitoring of tumor formation and progression in vivo in a variety of animal model systems. Power Doppler sonography is commonly used to assess and quantify blood flow velocities in tumors and lymph nodes The combination of these two modalities is useful in quantifying tumorinduced alterations of circulatory flow [10,11,12,13]
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