Feature | February 13, 2015

MR-Guided Focused Ultrasound Reverses Alzheimer’s Symptoms in Mice

Microbubbles open blood-brain barrier for more effective delivery of drugs to brain

MR guided focused ultrasound, Alzheimer's, mice, contrast media

The image on the left shows the plaque abnormalities on untreated transgenic mice and the image on the right shows the brain of a transgenic mouse that has been treated with MR imaging-guided focused ultrasound. Image courtesy of Kullervo Hynynen, Sunnybrook Research Institute.

February 13, 2015 — For the first time, researchers have reversed some of the symptoms of Alzheimer’s disease in mice using magnetic resonance (MR) imaging-guided focused ultrasound.

MR imaging-guided focused ultrasound has been shown to temporarily open the blood-brain barrier (BBB), which allows for more effective delivery of drugs to the brain. In order to accomplish this, researchers use a microbubble contrast agent. The microbubbles vibrate when they pass through the ultrasound beam, temporarily creating an opening in the BBB for the drugs to pass through. In addition, this combination of ultrasound and microbubbles has been shown to increase the number of new neurons and the dendrite length.

In this study, Kullervo Hynynen, Ph.D., a medical physicist at Sunnybrook Research Institute in Toronto, and his collaborators studied the effects of using MR imaging-guided focused ultrasound on the hippocampus of transgenic (TgCRND8) mice. Mice with this genetic variant have increased plaque on their hippocampus, the part of the brain that helps convert information from short-term to long-term memory; they also display symptoms similar to Alzheimer’s such as memory impairment and learning reversal. Thus, transgenic mice are used as an animal model for Alzheimer’s disease.

The researchers used MR imaging-guided focused ultrasound with microbubbles to open the BBB and treat the hippocampus of the mice. The researchers treated each side separately to be as accurate as possible in their focus of the ultrasound beam. They found the treatment led to improvements in cognition and spatial learning in the transgenic mice, potentially caused by reduced plaque and increased neuronal plasticity due to the focused ultrasound treatment. They found no tissue damage or negative behavioral changes in the mice due to the treatments in either the transgenic mice or the control (nontransgenic) mice. Both groups of mice benefited from increased neuronal plasticity, which confirms the previous research on the effects of MR imaging-guided focused ultrasound on plasticity in healthy mice.

An estimated 5.2 million Americans suffer from Alzheimer’s. It is the sixth leading cause of death in the United States and there is currently no treatment for the disease. “The results are an exciting step in the search for Alzheimer’s treatments,” said Steven Krosnick, M.D., program director for image-guided interventions at the National Institute of Biomedical Imaging and Bioengineering at NIH, “but there is more to be done. There are limitations on the memory tests that can be done on mice, and human cognition is significantly more complex. Hopefully these results will open doors to more research on how MR imaging-guided focused ultrasound could benefit cognition and perhaps be magnified by using other therapeutics in conjunction with this method.”

For more information: www.nibib.nih.gov

Related Content

Chest X-ray from a patient included in the study. Posteroanterior view, of a 79-year-old man with history of a previous pacemaker, with abandoned right atrial and right ventricular pacing leads on the right side at time of new cardiac resynchronization therapy defibrillator implant on the left side. Arrows indicate a nodular opacity in the right midlung concerning for mass. Find more images of patients in this study in Radiology: Cardiothoracic Imaging.

Chest X-ray from a patient included in the study. Posteroanterior view, of a 79-year-old man with history of a previous pacemaker, with abandoned right atrial and right ventricular pacing leads on the right side at time of new cardiac resynchronization therapy defibrillator implant on the left side. Arrows indicate a nodular opacity in the right midlung concerning for mass. Find more images of patients in this study in Radiology: Cardiothoracic Imaging.

Feature | Magnetic Resonance Imaging (MRI) | October 27, 2020
October 27, 2020 – Magn...
Nearly 40 MRIdian-focused presentations will be part of the ASTRO Scientific Sessions
News | Magnetic Resonance Imaging (MRI) | October 26, 2020
October 26, 2020 — ViewRay, Inc. announced that the company's MRIdian Linac MRI-guided radiation therapy system will
An example of a HeartFlow FFR-CT image showing the blood flow through what looked like a significant blockage on CT angiography alone, actually was not flow-limiting based on computational fluid dynamics. Use of the technology was supposed to reduce the number of diagnostic catheterizations in the FORECAST trial, but the costs of FFR-CT were not offset enough to show cost savings.

An example of a HeartFlow FFR-CT image showing the blood flow through what looked like a significant blockage on CT angiography alone, actually was not flow-limiting based on computational fluid dynamics. Use of the technology was supposed to reduce the number of diagnostic catheterizations in the FORECAST trial, but the costs of FFR-CT were not offset enough to show cost savings.

Feature | CT Angiography (CTA) | October 23, 2020
October 22, 2020 – In the FORECAST randomized clinical trial, the use of ...
This illustration show the complexity of the data obtained from one single patient with moderate/severe traumatic brain injury. Different imaging approaches and techniques have their own unique sensitivity in assessing different aspects of neuroanatomy and neuropathology. What can be seen on images also changes with time since injury. Data from comprehensive clinical and functional assessments using a range of other tools is also important for evaluating patient outcome. Through data harmonization and large

This illustration show the complexity of the data obtained from one single patient with moderate/severe traumatic brain injury. Different imaging approaches and techniques have their own unique sensitivity in assessing different aspects of neuroanatomy and neuropathology. What can be seen on images also changes with time since injury. Data from comprehensive clinical and functional assessments using a range of other tools is also important for evaluating patient outcome. Through data harmonization and large-scale analyses of data combined across multiple research sites, the ENIGMA Brain Injury will develop and test methods and procedures for making sense of the complexity in this data. Images courtesy of Olsen et al., Brain Imaging and Behavior, 2020

News | Magnetic Resonance Imaging (MRI) | October 23, 2020
October 23, 2020 — Trau...
The fMRI hyperscanning environment.

(A) The fMRI hyperscanning environment. The clinician (1) and patient (2) were positioned in two different 3T MRI scanners. An audio-video link enabled online communication between the two scanners (3), and video images were used to extract frame-by-frame facial expression metrics. During simultaneous acquisition of blood oxygen level–dependent (BOLD)–fMRI data, the clinician used a button box (4) to apply electroacupuncture (EA) treatment (real/sham, double-blind) to the patient (5) to alleviate evoked pressure pain to the leg (6; Hokanson cuff inflation). Pain and affect related to the treatment were rated after each trial. (B) Study overview. After an initial behavioral visit, each individual participated in a Clinical-Interaction (hyperscan preceded by a clinical intake) and No-Interaction condition (hyperscan without a preceding intake), in a counterbalanced order, with two different partners. (C) Experimental protocol. Each hyperscan was composed of 12 repeated trials (four verum EA, four sham EA, and four no treatment) in a pseudo-randomized order. After a resting period (far left), both participants were shown a visual cue to indicate whether the next pain stimulus would be treated (green frame) or not treated (red frame) by the clinician. These cues prompted clinicians prepare to either apply or not apply treatment while evoking corresponding anticipation for the patient. Following the anticipation cue, moderately painful pressure pain was applied to the patient’s left leg, while the clinician applied or did not apply treatment, respectively. After another resting period, participants rated pain (patients), vicarious pain (clinicians), and affect (both) using a visual analog scale (VAS).

News | Clinical Trials | October 22, 2020
October 22, 2020 — The potential impact of the patient-clinician relationship on a patient's response to treatment is
The FDA clearance, Quantib’s 6th to date, marks the first time a comprehensive AI prostate solution will be available to radiologists in the United States
News | Prostate Cancer | October 21, 2020
October 21, 2020 — Quantib, a market leader in...
Lesion was originally reported as indeterminate enhancing mass, and outside report recommended biopsy. Classic features of benign hemangioma are shown. Error was attributed to faulty reasoning. A, Axial MR image obtained 5 minutes after contrast agent administration shows peripheral nodular discontinuous enhancement. B, Axial MR image obtained 10 minutes after contrast agent administration shows centripetal progression of enhancement (arrow). C, Axial fast imaging employing steady-state acquisition (FIESTA)

Lesion was originally reported as indeterminate enhancing mass, and outside report recommended biopsy. Classic features of benign hemangioma are shown. Error was attributed to faulty reasoning. A, Axial MR image obtained 5 minutes after contrast agent administration shows peripheral nodular discontinuous enhancement. B, Axial MR image obtained 10 minutes after contrast agent administration shows centripetal progression of enhancement (arrow). C, Axial fast imaging employing steady-state acquisition (FIESTA) MR image shows lesion is homogeneously hyperintense compared with liver parenchyma. Image courtesy of American Roentgen Ray Society (ARRS), American Journal of Roentgenology (AJR)

News | Magnetic Resonance Imaging (MRI) | October 21, 2020
October 21, 2020 — According to an artic...
Flowchart of patient inclusion and exclusion.

Figure 1. Flowchart of patient inclusion and exclusion.

News | Coronavirus (COVID-19) | October 20, 2020
October 20, 2020 — A new multi-institutional study published in the journal ...
Ezra, a NY-based startup transforming early cancer screening using magnetic resonance imaging (MRI), announced that it has received FDA 510(k) premarket authorization for its Artificial Intelligence, designed to decrease the cost of MRI-based cancer screening, assisting radiologists in their analysis of prostate MRI scans. It is the first prostate AI to be cleared by the FDA.
News | Artificial Intelligence | October 20, 2020
October 20, 2020 — Ezra, a NY-based startup transforming early cancer screening using...