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.

This protocol is for studies that are approved by the ethics committee of the Charit&#233; - Universit&#228;tsmedizin Berlin (approval number: EA1/222/17, 2018/01/08) and the Data Protection Division and Corporate Governance of the Charit&#233; - Universit&#228;tsmedizin Berlin. Informed consent has been obtained from all subjects prior of being included in the study.
1. Subjects
NOTE: Recruitment of MS patients usually takes place at few days up to some weeks prior t...

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 t...

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 border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<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...

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 ...

This technical approach can be employed to study cerebral white and gray matter lesions in MS patients with greater detail at 7.0 Tesla. The main advantage is that we can examine brain changes with greater detail at 7.0 Tesla compared to lower magnetic field strengths. The enhanced spatial resolution is made possible by the increased signal-to-noise ratio and by the sensitivity gain at 7.0 Tesla.Disseminating these methods will be significant as they should provide the foundation for other researchers that are starting MS studies at 7.0 Tesla, and that's the main goal is to gain further insight into the MS pathology. Demonstrating the procedure will be Antje Els, a radiographer and study nurse from our facility. When the subject is ready, accompany them to the 7T MR scanner room and ask the subject to lie on the scanning table using pillows, blade cushions, and blankets to make the subject as comfortable as possible.Connect an MRI safe pulse oximeter to the subject and provide ear plugs and a handheld squeeze ball to be used during the examination in the case of emergency. Ask the subject to move closer to the radio frequency head coil and have the subject close their eyes while the table is moved very slowly until the laser positioning is in full alignment with the marker cross on top of the coil. After saving this position, move the subject table very slowly to the ISO center of the MR scanner while explaining to the subject that any side effects should resolve as soon as the table comes to a halt.After leaving the scanner room, use the intercom to confirm audible communication with the subject within the scanner. Before acquiring the scanning data, enter the required subject details, including the subject ID, date of birth, sex, age, and weight, as well as the study details such as the study name, institution, and individual performing the MR investigation. Select localizer and mark the sequence.Select options and adjustments and select go under the frequency tab. Under the transmitter tab, set the voltage as appropriate for the radio frequency coil and amplifier being used and click apply. Under a 3D shim, select measure.When the B0 map is generated, select calculate to acquire the shim values. When the shim values are consistent with the previous value, make sure that the basic frequency is re-centered and select apply and close. Then using at least three slices per orientation, make sure that all of the channels have been selected and press apply to run the localizer sequence in the sagittal, transversal, and coronal orientations.To acquire a 3D MPRAGE sequence, use the zoom and panning tool to zoom in and move the field of view on the localizer images and the adjustment volume. Make sure that all of the channels are selected and click apply to acquire the sequence in the sagittal orientation in alignment with the interhemispheric fissure. To run a FLAIR sequence, copy the geometry of the field of view in the same sagittal orientation and adjustment volume as for the MPRAGE scan, taking care of that the phase encoding is in the anterior to posterior direction and that all of the channels are selected and press apply to start the scan.To run a FLASH-ME, adjust the field of view according to the anatomy of the subject using the 3D MPRAGE and localizer images to plan the geometry and using the zoom and panning tool to manually adjust the field of view such that the entire head is in the middle. Tilt the head such that the lower boundary of the field of view is in line with the lower corpus callosum line before adjusting the uppermost layer end with the skull callate. Modify the adjustment volume if it's no longer aligned with the geometry volume and rerun the manual 3D shimming and frequency adjustments before clicking apply to run the sequence.For susceptibility-weighted imaging, rearrange the field of views such that the slice slab is shifted in the cranial direction and the uppermost border is aligned with the skull callate. Displace the slab in the ventral or dorsal direction so that the brain is completely in the middle of field of view. Modify the adjustment volume if it is no longer aligned with the geometry volume and rerun the manual 3D shimming and frequency adjustments before clicking apply to start the scan.For quantitative susceptibility mapping, move the slice stack cranially so that the top layer is aligned with the skull callate and rerun the manual 3D shimming and frequency adjustments to make sure that all of the channels are selected. Then click apply to run the sequence. For diffusion-weighted imaging, select a 2D echo planar imaging sequence and use the localizer images to plan the geometry in the transversal orientation without introducing any angulation.Move the field of view such that the upper line of the layer block is aligned with the skull callate. When the brain is exactly in the middle of the field of view, make sure that the phase encoding is in the anterior to posterior direction, that 64 different diffusion encoding directions are selected, and that the B values are set to 0 and 1, 000 seconds per square millimeter before clicking apply to run the sequence. To cancel any distortion artifacts, acquire the same echo planar imaging sequence, but using the reverse polarity of the phase encoding direction using the version of the echo planar imaging sequence with the phase encoding in the posterior to anterior direction.Set the direction to 180 degrees if necessary and confirm that 64 different diffusion encoding directions are selected, but only one B value at zero seconds per square millimeter, which will significantly reduce the scan time, but will be sufficient to correct any distortion artifacts during post-processing. Then click apply to run the sequence. As soon as the last sequence has finished and been reconstructed, the MRI examination will be ready.When all of the images have been completely acquired, move the subject table slowly away from the ISO center of the scanner and check in with the subject regarding any side effects from during or after the measurements. In this analysis, a 26-year-old woman diagnosed with relapsing remitting MS was examined at 7.0 Tesla as demonstrated. Some distortions in the B1 plus profile can be observed in the MR images, which is anticipated when moving to higher resonance frequencies as shorter wavelengths increase the destructive and constructive interferences.As observed, sagittal and transversal views provide different contrasts in the brain images. Although the MS diagnosis was subsequently challenged due to an increase in T2 lesions and multiple clinical relapses with incomplete remission, 7T MRI supported the MS diagnosis by revealing the central vein sign in the majority of paraventricular and juxtacortical lesions. The MS diagnosis was further corroborated by cortical pathology and hypointense rim structures surrounding a subset of T2 hyperintense lesions.These techniques are derived from strong collaborations between MR physics, imaging sciences, neurology specialists and neuro radiology experts and provide new MS-specific neuroimaging markers, such as a central vein sign and hypointense rim structures on T2 style weighted images.

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

Research

JoVE Journal

Medicine

8.3K vistas.  Max Delbrück Center for Molecular Medicine in the Helmholtz Association. Este enfoque técnico se puede emplear para estudiar las lesiones cerebrales de materia blanca y gris en pacientes con EM con mayor detalle a 7.0 Tesla. La principal ventaja es que podemos examinar los cambios cerebrales con mayor detalle a 7.0 Tesla en comparación con las intensidades de campo magnético más bajas. La resolución espacial mejorada es posible gracias al aumento de la relación señal-ruido y por la ganancia de sensibilidad a 7.0 Tesla.La difusión de estos métodos s...