Name: An Ultrasound-Guided Injection of Therapeutic Drugs into Human Salivary Glands
Uploaded: 2024-05-31T12:08:16
Description: All procedures involving human participants have been performed in compliance with the institutional, national, and international guidelines for human ...

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All procedures involving human participants have been performed in compliance with the institutional, national, and international guidelines for human welfare and have been reviewed by the local institutional review board.
1. Procedure&#8203;
<ol>
	<li>BoNT-A preparation NOTE: The abobotulinumtoxinA is a botulinum toxin type A of the Clostridium botulinum complex-hemagglutinin. It is a powder for solution for intramuscular or subcutaneous injection.
	<ol>
		<li>For the treatment of sialorrhea in adults, reconstitute 500 IU abobotulinumtoxinA with 2 mL of 0.9% sodium chloride solution for injection in order to obtain a solution containing 250 IU/mL of abobotulinumtoxinA.</li>
		<li>Administer a total of 250 IU of abobotulinumtoxinA per patient as follows: 50 IU in each submandibular gland and 75 IU in each parotid gland. In this way treat two patients with a single vial to avoid drug wastage.</li>
	</ol>
	</li>
	<li>Patients&#39; preparation&#8203;
	<ol>
		<li>After an adequate explanation of the procedure and of the potential risks and benefits of the treatment, obtain written informed consent from the patient.</li>
		<li>Place the patient on the ultrasound table in the supine position and possibly with the neck extended. 
		NOTE: Consider that not all neurological conditions leading to sialorrhea allow for the complete extension of the neck.</li>
		<li>Disinfect the skin in the area over the parotid and the submandibular glands with an antiseptic. Anesthetize each skin access site with ethylene chloride spray.</li>
	</ol>
	</li>
	<li>Ultrasound guidance 
	&#8203;NOTE: An ultrasound-guided procedure with a linear transducer (5 - 10 MHz) is used for gland localization in order to obtain real-time visualization of muscles, glands, bigger vessels or salivary ducts, and other surrounding structures, as well as of the correct needle position within the glandular tissue.
	<ol>
		<li>Turn on the ultrasound system and press the &#34;Start-end&#34; button to begin the exam.</li>
		<li>Press the &#34;Probe&#34; button to select the high frequency probe (5 - 10 MHz).</li>
		<li>Press the &#34;Patient&#34; button and insert the patient&#39;s name and surname.</li>
		<li>Press the &#34;Protocol&#34; button to select the appropriate protocol and sub-protocol (i.e., protocol: &#34;small tissues&#34;, sub-protocol: &#34;general&#34;).</li>
		<li>Press the &#34;Depth&#34; button and specify the depth of view to 5 cm.</li>
		<li>Press the &#34;Focus&#34; button to select the maximum detail of 2 cm.</li>
		<li>Place the transducer under the mandible, between the anterior and posterior bellies of the digastric muscle, to visualize the submandibular gland, which appears as a hypoechoic area with homogeneous echotexture compared to the surrounding tissues. 
		NOTE: Consider the submandibular gland ideally divided into two quadrants, one cranial and one caudal. Identify the widest gland diameter for the lateral needle access.</li>
		<li>Place the transducer below the external acoustic meatus to visualize the parotid gland, which appears as a hypoechoic area with homogeneous echotexture compared to the surrounding tissues. 
		NOTE: Consider the parotid gland ideally divided into four quadrants, two cranial and two caudal. Identify the two access sites for injection midway between the external auditory canal and the mandible angle, one in the cranial part and one in the caudal part of the gland (Figure 1).</li>
	</ol>
	</li>
</ol>
2. BoNT-A injection
NOTE: Use a 22 G needle for injections, with needle penetration at least 0.5 cm from the transducer. The transducer must be oriented longitudinally to the needle so that the needle is visible as a bright echoic line. In this way, the penetration of the needle into the soft tissues can be monitored during the procedure as the needle tip proceeds towards the target, preventing injuries to neurovascular structures.
<ol>
	<li>Use a lateral short-access approach at the widest gland diameter to access the submandibular gland.</li>
	<li>Inject 25 IU BoNT-A into the upper submandibular quadrant. After the injection, slightly retract the needle and change the direction of the needle tip towards the lower submandibular quadrant, injecting 25 IU BoNT-A for a total of 50 IU to each submandibular gland. 
	NOTE: In this way, two submandibular areas (cranial and caudal) are injected, providing a widespread diffusion of the drug within the glandular tissue.</li>
	<li>Use two access sites for the parotid gland injection. Identify the two accesses midway between the external auditory canal and the mandible angle, one in the cranial part of the gland and one in the caudal part of the gland.</li>
	<li>Using the upper access (in the cranial part of the gland), inject 18 - 19 IU BoNT-A into the medial-cranial quadrant. After the injection, slightly retract the needle, without leaving the site of the cranial part of the gland, and change the direction of the needle tip towards the lateral-cranial quadrant; inject 18 - 19 IU BoNT-A.</li>
	<li>Using the lower access (in the caudal part of the gland), inject 18 - 19 BoNT-A IU into the medial-caudal quadrant. After the injection, slightly retract the needle, without leaving the site of the caudal part of the gland, and change the direction of the needle tip towards the lateral-caudal quadrant; inject 18 - 19 IU BoNT-A. 
	NOTE: In this way, four parotid areas (medial-cranial, lateral-cranial, medial-caudal and lateral-caudal) are injected with a total of 75 IU BoNT-A, providing a widespread diffusion of the drug within the glandular tissue.</li>
	<li>After each injection, dab any bleeding with sterile gauze for 1 - 2 min. Re-evaluate the patient after one hour for any potential adverse events. Administer a nonsteroidal anti-inflammatory drug in case of persisting pain. Schedule a follow-up examination after 1 month.</li>
</ol>

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>abobotulinumtoxinA (Dysport)</td>
			<td>IpsenBiopharm, Wrexham, UK</td>
			<td></td>
			<td>Delivered drug</td>
		</tr>
		<tr>
			<td>MyLab Twice</td>
			<td>Esaote</td>
			<td></td>
			<td>Ultraonograph</td>
		</tr>
		<tr>
			<td>LA523 5&#8211;10 MHz</td>
			<td>Esaote</td>
			<td></td>
			<td>Linear transducer</td>
		</tr>
	</tbody>
</table>

an ultrasound-guided injection of therapeutic drugs into human salivary glands

Source: Barbero, P., et al,&#160;<a href="https://app.jove.com/v/54606">Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea.</a> J. Vis. Exp. (2016)
The video demonstrates an ultrasound-guided injection technique for administering therapeutic drugs into the salivary glands of a human patient.

<img alt="Figure 1" src="/files/ftp_upload/22268/22268_Figure1.jpg" /> 
Figure 1: Representation of the Ideal Injection Sites. A) Schematic division of the parotid gland into four quadrants, two cranial and two caudal, for correct injection into four different glandular sites. B) Schematic division of the submandibular gland into one cranial and one caudal quadrant for correct injection into two different glandular sites.

An Ultrasound-Guided Injection of Therapeutic Drugs into Human Salivary Glands

All procedures involving human participants have been performed in compliance with the institutional, national, and international guidelines for human ...

Begin by having the patient, with their mouth open, lie on an ultrasound table, in a supine position with the neck extended.
Disinfect and anesthetize the areas surrounding the enlarged submandibular gland and parotid gland.
Apply ultrasound gel for enhanced ultrasound wave transmission.
Place a high-frequency ultrasound probe under the mandible between the neck muscles to visualize the submandibular gland, which appears dark compared to surrounding tissues.
Guided by real-time visualization of the needle position, which appears as a bright line, inject the therapeutic drug accurately into the upper and lower areas of the submandibular gland, facilitating widespread drug diffusion within the tissue.
Next, place the probe under the ear canal to visualize the parotid gland, which appears darker than the surrounding tissues.
Identify the upper and lower access sites for the parotid gland injection. With real-time ultrasound guidance, inject the drug into gland quadrants to distribute it throughout the tissue.
Following injection, allow the patient to recover and assess for any possible adverse effects.

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Research

JoVE Encyclopedia of Experiments

Immunology

Immunotherapy

Immunogenics and Vaccine Development

68 Views. Source: Barbero, P., et al, Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea. J. Vis. Exp. (2016) The video demonstrates an ultrasound-guided injection technique for administering therapeutic drugs into the salivary glands of a human patient. 

Video: An Ultrasound-Guided Injection of Therapeutic Drugs into Human Salivary Glands - Concept

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the limitations of current treatments, as the majority of patients do not respond to immunotherapy. Development of accurate preclinical models to quickly identify novel and effective therapeutic combinations are critical to address this unmet clinical need. Pancreatic ductal adenocarcinoma (PDA) is a canonical example of an immune checkpoint blockade resistant tumor with only 2% of patients responding to immunotherapy. The genetically engineered KrasG12D+/-;Trp53R172H+/-;Pdx-1 Cre (KPC) mouse model of PDA recapitulates human disease and is a valuable tool for assessing therapies for immunotherapy resistant in the preclinical setting, but time to tumor onset is highly variable. Surgical orthotopic tumor implantation models of PDA maintain the immunobiological hallmarks of the KPC tissue-specific tumor microenvironment (TME) but require a time-intensive procedure and introduce aberrant inflammation. Here, we use an ultrasound-guided orthotopic tumor implantation model (UG-OTIM) to non-invasively inject KPC-derived PDA cell lines directly into the mouse pancreas. UG-OTIM tumors grow in the endogenous tissue site, faithfully recapitulate histological features of the PDA TME, and reach enrollment-sized tumors for preclinical studies by four weeks after injection with minimal seeding on the peritoneal wall. The UG-OTIM system described here is a rapid and reproducible tumor model that may allow for high throughput analysis of novel therapeutic combinations in the murine PDA TME.

We describe a protocol for the ultrasound guided implantation of murine-derived pancreatic ductal adenocarcinoma cell lines directly into the native tumor site. This approach resulted in pancreatic tumors detectable by ultrasound scanning within 2-4 weeks of injection, and significantly reduced the proportion tumor cell seeding on the peritoneal wall as compared to surgical orthotopic implantation.

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the ...

JoVE Journal

Cancer Research

Delivery of Antibodies into the Brain Using Focused Scanning Ultrasound

Only a small fraction of therapeutic antibodies targeting brain diseases are taken up by the brain. Focused ultrasound offers a possibility to increase uptake of antibodies and engagement through transient opening of the blood-brain barrier (BBB). In our laboratory, we are developing therapeutic approaches for neurodegenerative diseases in which an antibody in various formats is delivered across the BBB using microbubbles, concomitant with focused ultrasound application through the skull targeting multiple spots, an approach we refer to as scanning ultrasound (SUS). The mechanical effects of microbubbles and ultrasound on blood vessels increases paracellular transport across the BBB by transiently separating tight junctions and enhances vesicle- mediated transcytosis, allowing antibodies and therapeutic agents to effectively cross. Moreover, ultrasound also facilitates the uptake of antibodies from the interstitial brain into brain cells such as neurons where the antibody distributes throughout the cell body and even into neuritic processes. In our studies, fluorescently labeled antibodies are prepared, mixed with in-house prepared lipid-based microbubbles and injected into mice immediately before SUS is applied to the brain. The increased antibody concentration in the brain is then quantified. To account for alterations in normal brain homeostasis, microglial phagocytosis can be used as a cellular marker. The generated data suggest that ultrasound delivery of antibodies is an attractive approach to treat neurodegenerative diseases.

Presented here is a protocol to transiently open the blood-brain barrier (BBB) either focally or throughout a mouse brain to deliver fluorescently-labeled antibodies and activate microglia. Also presented is a method to detect the delivery of antibodies and microglia activation by histology.

Only a small fraction of therapeutic antibodies targeting brain diseases are taken up by the brain. Focused ultrasound offers a possibility to increase ...

Neuroscience

International Expert Consensus and Recommendations for Neonatal Pneumothorax Ultrasound Diagnosis and Ultrasound-guided Thoracentesis Procedure

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

Pneumothorax is a common emergency and critical disease in newborn infants that needs rapid, clear diagnosis and timely treatment. Diagnosis and treatment based on chest X-rays are associated with delayed management and radiation damage. Lung ultrasound (US) provides useful guidance for rapid, accurate diagnosis and the precise thoracentesis of pneumothorax.

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic ...

An Ultrasound-Guided Injection of Therapeutic Drugs into Human Salivary Glands

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