APA Sample-MRI Technology Thesis Proposal

Running Head: THE MOUSE MODEL OF TRAUMATIC BRAIN INJURY

Simultaneous Gadolinium-MRI and 18F-PBR111-PET in a mouse model of traumatic brain

injury.

Name

Institution

THE MOUSE MODEL IN TBI

Introduction

Traumatic Brain Injury, commonly known as the TBI, is the condition of the brain that

results when the external force cause a distortion in the head, causing the brain to collide with the

skull, making it to contract bruises or break the nerve fibers within it. Over the years, the mouse

has been observed to possess the same body conditions as humans do. For instance, the mouse

contracts diseases similar to human beings, such as cardiovascular diseases, cancer as well as

diabetes. Due to this nature of their body, scientists and researchers have come to conclude that

the mouse can be used as a model to study the human health conditions. The advanced detection

of traumatic brain Injury uses the Simultaneous Gadolinium-MRI and the Positron emission

Tomography imaging, commonly referred to as 18F-PBR111-PET.

Gadolinium is a chemical compound that forms trivalent ions with fluorescent properties.

Over decades, it has become commonplace in medical diagnostics in making the results of

magnetic resonance imaging due to its fluorescent properties (Caravan, Ellison, McMurry, &

Lauffer, 1999).

The two types of Gadolinium based MRI that have been used in detecting Traumatic

Brain Injury are the Dynamic contrast-enhanced imaging (DCE) and Dynamic susceptibility

Contrast Imaging (DSC).

Aim

The aim is to assess blood brain barrier integrity changes resulting from a traumatic brain

injury. The dynamic changed in image signal intensity will be determined following the injection

of the gadolinium contrast agent Gadovist.

THE MOUSE MODEL IN TBI

Justification

Magnetic Resonance Imaging (MRI) has become one of the most common methods of

assessing the brain trauma within individuals. Based on its accuracy, magnetic resonance

imaging has become the most reliable tool for providing information in the brain injuries. Its

ability to adjust depending on the quality of the image required is what has made it the most

reliable approach of diagonizing images within the traumatized brain. The doctor is able to

produce T1 or T2 weighted images using the Magnetic Resonance imaging, depending on the

level of contrast he or she is interested with (Kim et al., 1994).The T1 and T2-Weighted imaging

entirely depends on the relaxation time of water molecules within the object of focus, to produce

a quality image. In order to reduce the relaxation period, the advancement of technology has led

to introduction of Gadolinium in the Magnetic Resonance Imaging Technology.

On the other hand, the Positron emission Tomography has been widely used to produce

images of a traumatized brain. Unlike the magnetic resonance imaging, the Positron emission

imaging relies on gamma radiation. The technology uses a gamma camera whose function is to

detect the radioisotope that emits positrons (Jarritt & Acton, 1996). The radioisotope is mainly

connected to a medical compound that possesses specific physical and anatomical properties.

The commonly used compound in this case is the fluorodeoxyglucose (Gambhir, 2002).Due to

its technology, the PET technology is less accurate compared to Magnetic Resonance Imaging.

However, it provides the most reliable information on the pathophysiological activities of the

object of focus.

In order to produce images of the highest quality and to get the most reliable information,

scientists have sought to combine the functions of magnetic Resonance Imaging and Positron

Emission Imaging in a single activity of detecting a Traumatic Brain Injury. As a result both

THE MOUSE MODEL IN TBI

technologies have been applied simultaneously, to produce the best images of a traumatized

brain. The Magnetic Resonance and Positron emission Tomography (MR/PET) has become the

result of combining both technologies.

The combination of MRI and PET technologies has resulted to a MR/PET scanner which

uses the characteristics of both technologies to produce images with detailed information using

the spatial and temporal correlation of images. The scanner performs better to give more details

of the image compared to the information obtained from sequential scanning using both

technologies. Although it is very accurate in providing information on traumatized parts of the

brain, the MR/PET device may not be reliable when it comes to certain types of neuroscience.

In order to determine its suitability for the same, the simultaneous MR/PET technology

has been introduced in the study of small animals, the mouse model being the most common

model. The use of MRI and PET is essential in scanning the TBI in these animals because The

combined system will be able to produce information on the structural, functional as well as

metabolic information on the focused areas of the traumatized brain, giving the most reliable

anatomical details necessary for development of the most reliable conclusions and effective

treatments (Schlemmer, Pichler, Krieg, & Heiss, W. D. (2009).

In this case, the Gadolinium-MRI will use the two aforementioned types, the Dynamic

contrast-enhanced imaging (DCE) and Dynamic susceptibility Contrast Imaging (DSC).The

DCE plays the role of detecting the response of the TBI to radiotherapy while the DSC plays the

role of exploiting the regional susceptibility induced signal loss caused by paramagnetic contrast

agents using the T2 weighted images (Kosior et al., 2007)

THE MOUSE MODEL IN TBI

Objectives

The main objective of this paper is to investigate the relationship between the concentration

of gadolinium in the MRI/PET and the contrast of the mage taken using the technology.

Methodology

The study will use the laboratory mice that have been subjected to experimental brain

injury. To keep the accuracy of the test, the force used to inflict the injury will be maintained at a

constant level. After the injury has been inflicted, the study will also involve injecting the 18F-

PBR111 which is the most common tracer for Positron Emission Tomography, and Gadovist,

which is the main Magnetic Resonance Imaging gadolinium contrast agent. The study will then

involve imaging the uptake of the two simultaneously, using both the Magnetic resonance

Imaging and Positron emission Tomography. In order to maintain the accuracy, the study will

use a total of 200ul of injection, composing 50ul of Gadovist and approximately 10MBq of 18F-

PBR 111.The 140ul of the injection will be made of saline. Additionally the study will maintain

a constant study time of 7 days and 4 weeks to take scans of the traumatized brains using the

MR/PET scans.

Equipment

In order to make a perfect study, the research sought to choose the most perfect

equipment to help in attaining the desired results of the study. In this case, the study chose

Bruker ClinScan MRI/PET scanner to acquire Magnetic Resonance Images. The scanner has

been known to be the most accurate due to its features. It operates using the Siemens Singo

VB17 software and comprises of a very strong 7-Tesla Magnetic Resonance Magnet. This

magnet remains the best when it comes to magnetic resonance imaging due to its BGA20-S

THE MOUSE MODEL IN TBI

gradients system and a 300mm ID bore magnet. To have the most reliable images, the study will

use a 40mm ID rat brain radiofrequency to take images of the traumatized brain.

Image Acquisition and Assessment

To analyse the MRI images, the mean curve tool was used in the Siemens MRI

workstation. Before the injection, the study will acquire 3D T1-weighted VIBE images from the

traumatized rat brains. After 15 minutes of injection, other images of the traumatized brain will

also be acquired.

Similarly, Positron Emission Tomography images were also acquired using a removable

PET insert. The insert is made up of 3 rings with 16 detector blocks made of 15 by 15 LSO

crystals in each Siemens IAW operated block.

Using the University of Tubingen PET reconstruction software, the images taken were

then reconstructed, displayed and analyzed using the Siemens Inveon Research Workplace. The

study will then acquire a sixty-minute (60 min) positron emission tomography.

THE MOUSE MODEL IN TBI

References

Caravan, P., Ellison, J. J., McMurry, T. J., & Lauffer, R. B. (1999). Gadolinium (III) chelates as

MRI contrast agents: structure, dynamics, and applications. Chemical reviews, 99(9), 2293-2352.

Gambhir, S. S. (2002). Molecular imaging of cancer with positron emission tomography. Nature

reviews. Cancer, 2(9), 683.

Jarritt, P. H., & Acton, P. D. (1996). PET imaging using gamma camera systems: A review.

Nuclear medicine communications, 17(9), 758-766.

Kim, B., Semelka, R. C., Ascher, S. M., Chalpin, D. B., Carroll, P. R., & Hricak, H. (1994).

Bladder tumor staging: comparison of contrast-enhanced CT, T1-and T2-weighted MR imaging,

dynamic gadolinium-enhanced imaging, and late gadolinium-enhanced imaging. Radiology,

193(1), 239-245.

Kosior, R. K., Kosior, J. C., & Frayne, R. (2007). Improved dynamic susceptibility contrast

(DSC)‐MR perfusion estimates by motion correction. Journal of Magnetic Resonance Imaging,

26(4), 1167-1172.

Schlemmer, H. P., Pichler, B. J., Krieg, R., & Heiss, W. D. (2009). An integrated MR/PET

system: prospective applications. Abdominal imaging, 34(6), 668.

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