Name: magnetic resonance imaging of multiple sclerosis at 7.0 tesla
Uploaded: 2021-02-19T14:00:00.000+00:00
Duration: 8 min 51 s
Description: Watch this Scientific Journal Video about Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla at JoVE.com

This project (T.N.) has received funding in part from the European Research Council (ERC) under the European Union&#39;s Horizon 2020 research and innovation program under grant agreement No 743077 (ThermalMR). The authors wish to thank the teams at the Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; at the The Swedish National 7T Facility, Lund University Bioimaging Center, Lund University, Lund, Sweden and at the ECOTECH-COMPLEX, Maria Curie-Sk&#322;odowska University, Lublin, Poland for technical and other assistance.

There are no competing financial interests to be declared.

The protocol presented here describes a series of MRI sequences with different contrasts that are typically used when examining MS patients at 7.0 T. Together with emerging technological developments, they provide the basis for explorations into more advanced applications in metabolic or functional imaging.
Aside from brain lesions, lesions in the spinal cord frequently affect MS patients causing motor, sensory and autonomic dysfunction. However spinal cord imaging, particularly at 7.0 T, is technically challenging113. Further developments in parallel transmission and parallel imaging are warranted to overcome the hurdles of distorted B1&#160;field profiles114.
The goal of this protocol is to disseminate and synergistically connect technology developments and clinical application across disciplinary domains. Aside from the expected enhancements in spatial and temporal resolution, opportunities from the changing physical characteristics of higher magnetic fields include better contrasts in susceptibility-weighted imaging (SWI) and phase-contrast techniques115, as well as imaging of X-nuclei such as sodium116,117 and fluorine118,119,120 for a more in depth assessment of the pathology as well as therapeutic monitoring.

Multiple sclerosis (MS) is the most common chronic inflammatory and demyelinating disease of the central nervous system (CNS) that causes pronounced neurological disability in younger adults and leads to long term disability1,2. The pathological hallmark of MS is the accumulation of demyelinating lesions that occur in the gray and white matter of the brain and also diffuse neurodegeneration in the entire brain, even in normal-appearing white matter (NAWM)3,4. MS pathology suggests that inflammation drives tissue injury at all stages of the disease, even during the progressive stages of disease5. The first clinical manifestations of MS are commonly accompanied by reversible episodes of neurological deficits and referred to as a clinically isolated syndrome (CIS), when only suggestive of MS6,7. In the absence of a clear-cut CIS, caution should be exercised in making an MS diagnosis: the diagnosis should be confirmed by follow-up and initiation of long-term disease-modifying therapies should be postponed, pending additional evidence8.
Magnetic resonance imaging (MRI) is an indispensable tool in diagnosing MS and monitoring disease progression9,10,11. MRI at magnetic field strengths of 1.5 T and 3 T currently represents a crucial diagnostic tool in clinical practice to detect spin-spin relaxation time weighted (T2) hyperintense lesions and establish accurate diagnosis of MS based on the current version of the 2017 McDonald criteria8. Diagnostic criteria for MS emphasize the need to demonstrate dissemination of lesions in space and time, and to exclude alternative diagnoses8,12. Contrast enhanced MRI is the only method to assess acute disease and acute inflammation8but increasing concerns regarding potential long-term gadolinium brain deposition could potentially restrict contrast application as an important diagnostic tool13,14,17. Additionally, the differentiation of MS lesions from brain white matter lesions of other origins can sometimes be challenging due to their resembling morphology at lower magnetic field strengths.
While MRI is certainly the best diagnostic tool for MS patients, MR examinations and protocols should follow guidelines of the Magnetic Resonance Imaging in MS group (MAGNIMS) in Europe18,19 or the Consortium of Multiple Sclerosis Centers (CMSC) in North America20 for the diagnosis, prognosis and monitoring of MS patients. Standardized quality control studies in accordance with the latest guidelines across different hospitals and countries are also crucial21.
MRI protocols tailored for MS diagnosis and disease progression monitoring comprise multiple MRI contrasts including contrast governed by the longitudinal relaxation time T1, the spin-spin relaxation time T2, the effective spin-spin relaxation time T2*, and diffusion weighted imaging (DWI)22. Harmonization initiatives provided consensus reports for MRI in MS to move towards standardized protocols that facilitate clinical translation and comparison of data across sites23,24,25. T2-weighted imaging is well established and frequently used in clinical practice for identification of white matter (WM) lesions, which are characterized by hyperintense appearance26,27. While being an important diagnostic criterion for MS28, the WM lesion load correlates only weakly with clinical disability, due to its lack of specificity for lesion severity and the underlying pathophysiology26,27,29. This observation has triggered explorations into parametric mapping of the transverse relaxation time T2 30. T2*-weighted imaging has become increasingly important in imaging MS. The central vein sign in T2* weighted MRI is considered to be a specific imaging marker for MS lesions27,31,32,33. T2* is sensitive to iron deposition34,35, which may relate to disease duration, activity and severity36,37,38. T2* was also reported to reflect brain tissue changes in patients with minor deficits and early MS, and thus may become a tool to assess the development of MS already at an early stage39,40.
Improvements in MRI technology promise to better identify changes in the CNS of MS patients and to provide clinicians with a better guide to enhance the accuracy and speed of an MS diagnosis11. Ultrahigh &#64257;eld (UHF, B0&#8805;7.0 T) MRI benefits from an increase in signal-to-noise ratio (SNR) that can be invested in enhanced spatial or temporal resolutions, both key to superior imaging for more accurate and definitive diagnoses41,42. Transmission field (B1+) inhomogeneities that are an adverse attribute of the 1H radio-frequency used at ultrahigh magnetic fields43 would benefit from multichannel transmission using parallel transmit (pTx) RF coils and RF pulse design approaches that enhance B1+ homogeneity and thus facilitate uniform coverage of the brain44.
With the advent of 7.0 T MRI, we have achieved more insight into demyelinating diseases such as MS with respect to increased sensitivity and specificity of lesion detection, central vein sign identification, leptomeningeal enhancement, and even with respect to metabolic changes45. MS lesions have long been shown from histopathological studies to form around veins and venules46. The perivenous distribution of lesions (central vein sign) can be identified with T2* weighted MRI46,47,48 at 3.0 T or 1.5 T, but can be best identified with UHF-MRI at 7.0 T49,50,51,52. Other than the central vein sign, UHF-MRI at 7.0 T has improved or uncovered MS-specific markers such as hypointense rim structures and differentiation of MS grey matter lesions53,54,55,56. A better delineation of these markers with UHF-MRI promises to overcome some of the challenges of differentiating MS lesions from those occurring in other neuroinflammatory conditions such as Susac syndrome53 and neuromyelitis optica54, while also identifying common pathogenetic mechanisms in other conditions or variants of MS such as Bal&#243;&#39;s concentric sclerosis57,58.
Recognizing the challenges and opportunities of UHF-MRI for the detection and differentiation of MS lesions, this article describes our current technical approach to study cerebral white and grey matter lesions in MS patients at 7.0 T using different imaging techniques. The up-to-date protocol includes the preparation of the MR setup including the radiofrequency (RF) coils tailored to the UHF-MR, standardized screening, safety and interview procedures with MS patients, patient positioning in the MR scanner and acquisition of brain scans dedicated to MS. The article is meant to guide imaging experts, basic researchers, clinical scientists, translational researchers, and technologists with all levels of experience and expertise ranging from trainees to advanced users and applications experts into the field of UHF-MRI in MS patients, with the ultimate goal of synergistically connecting technology development and clinical application across disciplinary domains.

<table><tbody><tr><td>7T TX/RX 24 Ch Head Coil</td><td>Nova Medical, Inc., Wilmington, USA</td><td>NM008-24-7S-013</td><td>1-channel circular polarized (CP) transmit (Tx), 24-channel receive (Rx) RF head coil</td></tr><tr><td>Magnetom 7T System</td><td>Siemens Healthineers, Erlangen, Germany</td><td>MRB1076</td><td>7.0 T whole body research scanner</td></tr><tr><td>syngoMR B17 Software</td><td>Siemens Healthineers, Erlangen, Germany</td><td>B17A</td><td>image processing software for the Magnetom 7T system</td></tr></tbody></table>

magnetic resonance imaging of multiple sclerosis at 7.0 tesla

The overall goal of this article is to demonstrate a state-of-the-art ultrahigh field (UHF) magnetic resonance (MR) protocol of the brain at 7.0 Tesla in multiple sclerosis (MS) patients. MS is a chronic inflammatory, demyelinating, neurodegenerative disease that is characterized by white and gray matter lesions. Detection of spatially and temporally disseminated T2-hyperintense lesions by the use of MRI at 1.5 T and 3 T represents a crucial diagnostic tool in clinical practice to establish accurate diagnosis of MS based on the current version of the 2017 McDonald criteria. However, the differentiation of MS lesions from brain white matter lesions of other origins can sometimes be challenging due to their resembling morphology at lower magnetic field strengths (typically 3 T). Ultrahigh field MR (UHF-MR) benefits from increased signal-to-noise ratio and enhanced spatial resolution, both key to superior imaging for more accurate and definitive diagnoses of subtle lesions. Hence, MRI at 7.0 T has shown encouraging results to overcome the challenges of MS differential diagnosis by providing MS-specific neuroimaging markers (e.g., central vein sign, hypointense rim structures and differentiation of MS grey matter lesions). These markers and others can be identified by other MR contrasts other than T1 and T2 (T2*, phase, diffusion) and substantially improve the differentiation of MS lesions from those occurring in other neuroinflammatory conditions such as neuromyelitis optica and Susac syndrome. In this article, we describe our current technical approach to study cerebral white and grey matter lesions in MS patients at 7.0 T using different MR acquisition methods. The up-to-date protocol includes the preparation of the MR setup including the radio-frequency coils customized for UHF-MR, standardized screening, safety and interview procedures with MS patients, patient positioning in the MR scanner and acquisition of dedicated brain scans tailored for examining MS.

A 26-year-old woman diagnosed with relapsing remitting MS (RRMS) was examined at 7.0 T using the above protocols (Figure 11). Some distortions in the B1+ profile can be observed in the MR images. This is anticipated when moving to higher resonance frequencies43; the shorter wavelengths increase destructive and constructive interferences105,106. To acquire the MR images (Figure 11, Figure 12, Figure 13, Figure 14), we used a single channel transmit volume coil on a Siemens 7.0 T MR system in which a manual adjustment of phase and amplitude was not possible to offset the B1+ inhomogeneities. Multi-transmit technologies offer the degrees of freedom of parallel transmission required to dynamically modulate the B1+ &#64257;eld distribution44. While the B1+ pattern cannot be modified for a single transmit element of a given coil, the electromagnetic properties of the surrounding environment may be altered, as has been shown with dielectric padding filled with water107 or calcium titanate suspensions108 used at 7.0 T. Geometrically tailored dielectric pads have been shown to be effective at imaging the brain 109,110 and particularly the inner ear111, a challenging place to image due to inhomogeneities from susceptibility differences between inner ear fluids and bone.
Shown in Figure 11 are sagittal and transversal views of the patient&#39;s brain using different protocols providing different contrasts. Four and a half years prior to the 7.0 T MR examination the patient presented with diplopia and blurry vision. Diagnosis was initially established, based on the 2017 McDonald criteria8 due to periventricular, juxtacortical and infratentorial MR lesion distribution and based on the occurrence of both gadolinium-enhancing and non-enhancing lesions at 3.0 T. CSF findings were within normal limits. Medication with natalizumab (NTZ) was subsequently initiated. The MS diagnosis was subsequently challenged due to an increase in T2 lesions and multiple clinical relapses with incomplete remission despite the highly efficacious NTZ treatment. However, 7.0 T MRI supported the MS diagnosis by revealing the central vein sign in the majority of periventricular and juxtacortical lesions (Figure 12). The MS diagnosis was further corroborated by cortical pathology (Figure 13) and hypointense rim structures surrounding a subset of T2 hyperintense lesions (Figure 14). The diagnostic re-evaluation also included a search for other autoimmune, infectious, and metabolic disorders but did not reveal further abnormal results. Eventually the patient was tested positive for antibodies against NTZ, indicating antibody-mediated neutralization and explaining the insufficient treatment response towards NTZ 112. Therefore, an MS diagnosis with an unresponsiveness towards NTZ therapy was concluded in this patient. Medication was switched from NTZ to Ocrelizumab and the patient has been relapse-free during the ensuing stages.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/62142/62142fig01.jpg" /> 
Figure 1. Switch box of Siemens MR scanner <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/62142/62142fig02.jpg" /> 
Figure 2. Connecting a dedicated RF coil to the MR system. (a) Transmit (Tx), 24- or 32 channel receive (Rx) radio frequency head coil tailored for brain MRI at 7.0 T (b) Instruct the subject to move closer to the RF head coil and position the head of the subject over the lower RX-coil and beneath the upper RX-coil (left panel). Next move the TX-part of the RF head coil over the RX-coil (bottom right). <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/62142/62142fig03.jpg" /> 
Figure 3. Running adjustments (Siemens system). (a) Basic frequency adjustment, (b) Transmitter voltage adjustment, (c) Generation of B0 Map and 3D shimming. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/62142/62142fig4v3.jpg" /> 
Figure 4. MR sequence planning on 7.0 T MR systems from different vendors. (a) Siemens, (b) Philips and (c) General Electric. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig4v2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/62142/62142fig05.jpg" /> 
Figure 5. Planning 3D MP2RAGE imaging sequence <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig05large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/62142/62142fig06.jpg" /> 
Figure 6. Planning 3D SPACE-FLAIR imaging sequence <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig06large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 7" class="xfigimg" src="/files/ftp_upload/62142/62142fig07.jpg" /> 
Figure 7. Planning 2D FLASH-ME imaging sequence <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig07large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 8" class="xfigimg" src="/files/ftp_upload/62142/62142fig08.jpg" /> 
Figure 8. Planning 3D susceptibility weighted imaging sequence <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig08large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 9" class="xfigimg" src="/files/ftp_upload/62142/62142fig09.jpg" /> 
Figure 9. Planning QSM-FC <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig09large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 10" class="xfigimg" src="/files/ftp_upload/62142/62142fig10.jpg" /> 
Figure 10. Planning diffusion-weighted echo-planar imaging sequence <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig10large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 11" class="xfigimg" src="/files/ftp_upload/62142/62142fig11.jpg" /> 
Figure 11. Representative results of high-resolution brain MRI of an RRMS patient Upper panel from left to right: (a) sagittal view of a T1w 3D inversion recovery-prepared spoiled-GRE sequence (MPRAGE), (b) transversal view of T1w 3D MPRAGE, (c) transversal view of T2*w 2D FLASH sequence with multi-echo readout (FLASH-ME), (d) transversal view of a T2w fluid-attenuated inversion recovery using sampling perfection with application-optimized contrasts using different flip angle evolutions (SPACE-FLAIR), (e) transversal view of flow compensated quantitative susceptibility mapping (QSM-FC). Lower panel from left to right: (f) sagittal view of a T1w 3D magnetization-prepared rapid gradient echo sequence (MP2RAGE), (g) transversal view of T1w 3D MP2RAGE, (h) transversal view of 3D susceptibility weighted imaging (SWI) using magnitude and phase data of a fully flow-compensated GE sequence, (i) combined fractional anisotropy map and directional map of an echo-planar diffusion-weighted imaging sequence (2D EPI), (j) transversal view of T2*w 2D gradient echo imaging with flow compensation (GRE-FC). <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig11large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 12" class="xfigimg" src="/files/ftp_upload/62142/62142fig12.jpg" /> 
Figure 12. Representative white-matter MS lesions with central vein sign (a and b) Transversal view of T2*w 2D FLASH sequence with multi-echo readout (FLASH-ME) reveals highly MS-specific central vein sign (red arrow) within exemplary periventricular lesions, (c) a right-hemispheric thalamic lesion (d), and a parietal juxtacortical lesion, substantiating the patient&#39;s MS diagnosis. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig12large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 13" class="xfigimg" src="/files/ftp_upload/62142/62142fig13.jpg" /> 
Figure 13. Representative cortical MS lesion. (a) Sagittal view of a T1w 3D magnetization-prepared rapid gradient echo sequence (MP2RAGE) delineates subpial cortical lesion (red arrow heads) within parietal cortex (b) with corresponding hyperintensity in transversal view of a T2w fluid-attenuated inversion recovery (SPACE-FLAIR), indicating the occurrence of cortical MS pathology in the relapsing-remitting MS patient. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig13large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 14" class="xfigimg" src="/files/ftp_upload/62142/62142fig14.jpg" /> 
Figure 14. Representative hypointense rim structures. (a) Transversal view of T2*w 2D FLASH sequence with multi-echo readout (FLASH-ME) reveals an ovoid periventricular MS lesion, and (b) transversal view of 3D susceptibility weighted imaging (SWI) delineates a hypointense rim structure around the lesion, suggesting iron-laden macrophages to be present as a potential surrogate for MS lesion activity. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/62142/62142fig14large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Metallic implants (can malfunction due to magnetic fields or cause injury)</td>
		</tr>
		<tr>
			<td>Electronic devices e.g. pacemakers, defibrillators, insulin pump, nerve stimulators</td>
		</tr>
		<tr>
			<td>Aneurysm and haemostatic clips, prosthetic heart valves</td>
		</tr>
		<tr>
			<td>Cochlear, otologic implants</td>
		</tr>
		<tr>
			<td>Drug infusion devices</td>
		</tr>
		<tr>
			<td>Deep brain stimulation electrodes</td>
		</tr>
		<tr>
			<td>Lead electrocardiogram wires</td>
		</tr>
		<tr>
			<td>Other contraindications (risk of skin burns, swelling or damage via magnetic field effects)</td>
		</tr>
		<tr>
			<td>Some medication patches</td>
		</tr>
		<tr>
			<td>Metallic foreign bodies e.g. shrapnel or other minute metal fragments in the eye</td>
		</tr>
		<tr>
			<td>Some tattoo and cosmetics (permanent makeup)</td>
		</tr>
		<tr>
			<td>Body piercing jewellery</td>
		</tr>
		<tr>
			<td>Pregnancy (possible adverse biological effects by magnetic fields)</td>
		</tr>
		<tr>
			<td>Known claustrophobia</td>
		</tr>
	</tbody>
</table>
Table 1. Principal contraindications of an MRI examination. The most common contraindications are metallic implants. Implants are becoming increasingly MR safe (MRI-conditional) but remain a major concern.

Watch this Scientific Journal Video about Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla at JoVE.com

Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla

Here, we present a protocol to acquire magnetic resonance (MR) images of multiple sclerosis (MS) patient brains at 7.0 Tesla. The protocol includes preparation of the setup including the radio-frequency coils, standardized interview procedures with MS patients, subject positioning in the MR scanner and MR data acquisition.

The overall goal of this article is to demonstrate a state-of-the-art ultrahigh field (UHF) magnetic resonance (MR) protocol of the brain at 7.0 Tesla in ...

magnetic-resonance-imaging-of-multiple-sclerosis-at-70-tesla

Nanyang Technological University

Research

JoVE Journal

Medicine

8.6K Views.  Max Delbrück Center for Molecular Medicine in the Helmholtz Association. Deze technische benadering kan worden gebruikt om cerebrale witte en grijze stof laesies bij MS-patiënten met meer detail te bestuderen bij 7,0 Tesla. Het belangrijkste voordeel is dat we hersenveranderingen met meer detail kunnen onderzoeken bij 7,0 Tesla in vergelijking met lagere magnetische veldsterktes. De verbeterde ruimtelijke resolutie wordt mogelijk gemaakt door de verhoogde signaal-ruisverhouding en door de gevoeligheidswinst bij 7,0 Tesla.Het verspreiden van deze methoden z...

Video: Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla

Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring 

Nanomedications can be carried by blood borne monocyte-macrophages into the reticuloendothelial system (RES; spleen, liver, lymph nodes) and to end organs. The latter include the lung, RES, and brain and are operative during human immunodeficiency virus type one (HIV-1) infection. Macrophage entry into tissues is notable in areas of active HIV-1 replication and sites of inflammation. In order to assess the potential of macrophages as nanocarriers, superparamagnetic iron-oxide and/or drug laden particles coated with surfactants were parenterally injected into HIV-1 encephalitic mice. This was done to quantitatively assess particle and drug biodistribution. Magnetic resonance imaging (MRI) test results were validated by histological coregistration and enhanced image processing. End organ disease as typified by altered brain histology were assessed by MRI. The demonstration of robust migration of nanoformulations into areas of focal encephalitis provides '"proof of concept" for the use of advanced bioimaging techniques to monitor macrophage migration. Importantly, histopathological aberrations in brain correlate with bioimaging parameters making the general utility of MRI in studies of cell distribution in disease feasible. We posit that using such methods can provide a real time index of disease burden and therapeutic efficacy with translational potential to humans.

Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring

Bioimaging methods used to assess cell biodistribution of nanoparticles are applicable for therapeutic and diagnostic monitoring of nanoformulated compounds. The methods described herein are sensitive and specific when assessed by histological coregistration. The methodologies provide a translational pathway from rodent to human applications.

Nanomedications can be carried by blood borne monocyte-macrophages into the reticuloendothelial system (RES; spleen, liver, lymph nodes) and to end ...

Bioengineering

Multiple-mouse Neuroanatomical Magnetic Resonance Imaging

The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly growing, motivated by the need for improved tools for characterizing and evaluating mouse models of human disease. MRI is an excellent modality for investigating genetically altered animals. It is capable of whole brain coverage, can be used in vivo, and provides multiple contrast mechanisms for investigating different aspects of neuranatomy and physiology. The advent of high-field scanners along with the ability to scan multiple mice simultaneously allows for rapid phenotyping of novel mutations.
Effective mouse MRI studies require attention to many aspects of experiment design. In this article, we will describe general methods to acquire quality images for mouse phenotyping using a system that images mice concurrently in shielded transmit/receive radio frequency (RF) coils in a common magnet (Bock et al., 2003). We focus particularly on anatomical phenotyping, an important and accessible application that has shown a high potential for impact in many mouse models at our imaging centre. Before we can provide the detailed steps to acquire such images, there are important practical considerations for both in vivo brain imaging (Dazai et al., 2004) and ex vivo brain imaging (Spring et al., 2007) that should be noted. These are discussed below.

Magnetic resonance imaging (MRI) has become an increasingly popular tool for examining the phenotype of genetically altered mice. This article illustrates the methods necessary to achieve high-throughput phenotyping of genetically altered mice using multiple-mouse MRI.

The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly growing, motivated by the need for improved tools for characterizing and ...

Neuroscience

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present applications are designed to investigate differences of WM involvement patterns in different brain diseases, especially neurodegenerative disorders, by use of different DTI analyses in comparison with matched controls. 	
DTI data analysis is performed in a variate fashion, i.e. voxelwise comparison of regional diffusion direction-based metrics such as fractional anisotropy (FA), together with fiber tracking (FT) accompanied by tractwise fractional anisotropy statistics (TFAS) at the group level in order to identify differences in FA along WM structures, aiming at the definition of regional patterns of WM alterations at the group level. Transformation into a stereotaxic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The present applications show optimized technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level. On this basis, FT techniques can be applied to group averaged data in order to quantify metrics information as defined by FT. Additionally, application of DTI methods, i.e. differences in FA-maps after stereotaxic alignment, in a longitudinal analysis at an individual subject basis reveal information about the progression of neurological disorders. Further quality improvement of DTI based results can be obtained during preprocessing by application of a controlled elimination of gradient directions with high noise levels.	
In summary, DTI is used to define a distinct WM pathoanatomy of different brain diseases by the combination of whole brain-based and tract-based DTI analysis.

Diffusion tensor imaging (DTI) basically serves as an MRI-based tool to identify in vivo the microstructure of the brain and pathological processes due to neurological disorders within the cerebral white matter. DTI-based analyses allow for application to brain diseases both at the group level and in single subject data.

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present ...

The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood 33. To help improve this understanding, proton magnetic resonance spectroscopy (1H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as &#947;-aminobutyric acid (GABA) and glutamate in a region-specific manner 41. In fact, a recent study demonstrated that 1H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration 34. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with 1H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices 27,30,31. Methodological factors to consider and possible modifications to the protocol are also discussed.

This article aims to describe a basic protocol for combining transcranial direct current stimulation (tDCS) with proton magnetic resonance spectroscopy (1H-MRS) measurements to investigate the effects of bilateral stimulation on primary motor cortex metabolism.

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of ...

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using non-invasive magnetic resonance imaging methods.

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of ...

Cardiac Magnetic Resonance Imaging at 7 Tesla

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher magnetic field strengths and potentially provides improved signal contrast and spatial resolution. While promising results have been achieved, ultra-high field CMR is challenging due to energy deposition constraints and physical phenomena such as transmission field non-uniformities and magnetic field inhomogeneities. In addition, the magneto-hydrodynamic effect renders the synchronization of the data acquisition with the cardiac motion difficult. The challenges are currently addressed by explorations into novel magnetic resonance technology. If all impediments can be overcome, ultra-high field CMR may generate new opportunities for functional CMR, myocardial tissue characterization, microstructure imaging or metabolic imaging. Recognizing this potential, we show that multi-channel radio frequency (RF) coil technology tailored for CMR at 7 Tesla together with higher order B0 shimming and a backup signal for cardiac triggering facilitates high fidelity functional CMR. With the proposed setup, cardiac chamber quantification can be accomplished in examination times similar to those achieved at lower field strengths. To share this experience and to support the dissemination of this expertise, this work describes our setup and protocol tailored for functional CMR at 7 Tesla.

The sensitivity gain inherent to ultrahigh field magnetic resonance holds promise for high spatial resolution imaging of the heart. Here, we describe a protocol customized for functional cardiovascular magnetic resonance (CMR) at 7 Tesla using an advanced multi-channel radio-frequency coil, magnetic field shimming and a triggering concept.

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher ...

Functional Magnetic Resonance Spectroscopy at 7 T in the Rat Barrel Cortex During Whisker Activation

Nuclear magnetic resonance (NMR) spectroscopy offers the opportunity to measure cerebral metabolite contents in vivo and noninvasively. Thanks to technological developments over the last decade and the increase in magnetic field strength, it is now possible to obtain good resolution spectra in vivo in the rat brain. Neuroenergetics (i.e., the study of brain metabolism) and, especially, metabolic interactions between the different cell types have attracted more and more interest in recent years. Among these metabolic interactions, the existence of a lactate shuttle between neurons and astrocytes is still debated. It is, thus, of great interest to perform functional proton magnetic resonance spectroscopy (1H-MRS) in a rat model of brain activation and monitor lactate. However, the methyl lactate peak overlaps lipid resonance peaks and is difficult to quantify. The protocol described below allows metabolic and lactate fluctuations to be monitored in an activated brain area. Cerebral activation is obtained by whisker stimulation and 1H-MRS is performed in the corresponding activated barrel cortex, whose area is detected using blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). All steps are fully described: the choice of anesthetics, coils, and sequences, achieving efficient whisker stimulation directly in the magnet, and data processing.

After checking by blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) that the corresponding somatosensory barrel field cortex area (called S1BF) is correctly activated, the main goal of this study is to quantify lactate content fluctuations in the activated rat brains by localized proton magnetic resonance spectroscopy (1H-MRS) at 7 T.

Nuclear magnetic resonance (NMR) spectroscopy offers the opportunity to measure cerebral metabolite contents in vivo and noninvasively. Thanks to ...

Diffusion Tensor Magnetic Resonance Imaging in Chronic Spinal Cord Compression

Chronic spinal cord compression is the most common cause of spinal cord impairment in patients with nontraumatic spinal cord damage. Conventional magnetic resonance imaging (MRI) plays an important role in both confirming the diagnosis and evaluating the degree of compression. However, the anatomical detail provided by conventional MRI is not sufficient to accurately estimate neuronal damage and/or assess the possibility of neuronal recovery in chronic spinal cord compression patients. In contrast, diffusion tensor imaging (DTI) can provide quantitative results according to the detection of water molecule diffusion in tissues. In the present study, we develop a methodological framework to illustrate the application of DTI in chronic spinal cord compression disease. DTI fractional anisotropy (FA), apparent diffusion coefficients (ADCs), and eigenvector values are useful for visualizing microstructural pathological changes in the spinal cord. Decreased FA and increases in ADCs and eigenvector values were observed in chronic spinal cord compression patients compared to healthy controls. DTI could help surgeons understand spinal cord injury severity and provide important information regarding prognosis and neural functional recovery. In conclusion, this protocol provides a sensitive, detailed, and noninvasive tool to evaluate spinal cord compression.

Here, we present a protocol for the application of diffusion tensor imaging parameters to evaluate spinal cord compression.

Chronic spinal cord compression is the most common cause of spinal cord impairment in patients with nontraumatic spinal cord damage. Conventional magnetic ...

Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis

Multiple sclerosis (MS) is a neuroinflammatory disease with expanding axonal and neuronal degeneration and demyelination in the central nervous system, leading to motor dysfunctions, psychical disability, and cognitive impairment during MS progression. Positron emission tomography (PET) is an imaging technique able to quantify in vivo cellular and molecular alterations.
Radiotracers with affinity to intact myelin can be used for in vivo imaging of myelin content changes over time. It is possible to detect either an increase or decrease in myelin content, what means this imaging technique can detect demyelination and remyelination processes of the central nervous system. In this protocol we demonstrate how to use PET imaging to detect myelin changes in the lysolecithin rat model, which is a model of focal demyelination lesion (induced by stereotactic injection) (i.e., a model of multiple sclerosis disease). 11C-PIB PET imaging was performed at baseline, and 1 week and 4 weeks after stereotaxic injection of lysolecithin 1% in the right striatum (4 &#181;L) and corpus callosum (3 &#181;L) of the rat brain, allowing quantification of focal demyelination (injection site after 1 week) and the remyelination process (injection site at 4 weeks).
Myelin PET imaging is an interesting tool for monitoring in vivo changes in myelin content which could be useful for monitoring demyelinating disease progression and therapeutic response.

Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis

This protocol has the aim of monitoring in vivo myelin changes (demyelination and remyelination) by positron emission tomography (PET) imaging in an animal model of multiple sclerosis.

Multiple sclerosis (MS) is a neuroinflammatory disease with expanding axonal and neuronal degeneration and demyelination in the central nervous system, ...

Cardiac Magnetic Resonance Imaging

Source: Frederick W. Damen and <a href="https://www-jove-com.remotexs.ntu.edu.sg/author/Craig+J._Goergen">Craig J. Goergen</a>, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana
In this video, high field, small-bore magnetic resonance imaging (MRI) with physiological monitoring is demonstrated to acquire gated cine loops of the murine cardiovascular system. This procedure provides a basis for assessing left-ventricular function, visualizing vascular networks, and quantifying motion of organs due to respiration. Comparable small animal cardiovascular imaging modalities include high-frequency ultrasound and micro-computed tomography (CT); however, each modality is associated with trade-offs that should be considered. While ultrasound does provide high spatial and temporal resolution, imaging artifacts are common. For example, dense tissue (i.e., the sternum and ribs) can limit imaging penetration depth, and hyperechoic signal at the interface between gas and liquid (i.e., pleura surrounding the lungs) can blur contrast in nearby tissue. Micro-CT in contrast does not suffer from as many in-plane artifacts, but does have lower temporal resolution and limited soft-tissue contrast. Furthermore, micro-CT uses X-ray radiation and often requires the use of contrast agents to visualize vasculature, both of which are known to cause side effects at high doses including radiation damage&#160; and renal injury. Cardiovascular MRI provides a nice compromise between these techniques by negating the need for ionizing radiation and providing the user with the ability to image without contrast agents (although contrast agents are often used for MRI).
This data was acquired with a triggering Fast Low Angle SHot (FLASH) MRI sequence that was gated off of the R-peaks in the cardiac cycle and expiratory plateaus in respiration. These physiological events were monitored through subcutaneous electrodes and a pressure-sensitive pillow that was secured against the abdomen. To ensure the mouse was properly warmed, a rectal temperature probe was inserted and used to control the output of a MRI-safe heating fan. Once the animal was inserted into the bore of the MRI scanner and navigation sequences were run to confirm positioning, the gated FLASH imaging planes were prescribed and data acquired. Overall, high field MRI is a powerful research tool that can provide soft tissue contrast for the study of small animal disease models.

Cardiac MRI: Principle and Imaging

Source: Frederick W. Damen and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana
In this video, high ...

Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla

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