Spectro

From CNI Wiki
Jump to navigation Jump to search

1. MRS in Neurosciences: In-vivo spectroscopy methods and applications at CNI

1.1 Overview

Discoveries about the brain have implications for fields ranging from Business, Law, Psychology, and Education. The interest of measuring metabolic changes via MRS techniques and combining that information with functional MRI measurements continues to grow. CNI continues to support the research of its user community by providing state-of-the art data acquisition and state-of-the-art data management and analysis capabilities for in-vivo spectroscopy. Through collaborative efforts the special interest spectroscopy group at CNI has enabled education, participated in experimental design, and guided analyses and interpretation of results.

Interest in measuring metabolic changes via MRS techniques and combining that information with functional MRI measurements in neuroscience studies continues to grow. CNI continues to support the research of its user community by developing and incorporating for general use new data acquisition and data analysis capabilities as recommended by the at-large MRS community. Through collaborative efforts, the special interest spectroscopy group at CNI has enabled education and participated in experimental design, guided analyses, and interpretation of results.

Link to most recent spectroscopy blog post is here - https://cni.su.domains/recent-advances-in-in-vivo-spectroscopy-at-cni/


Examples of studies at the CNI using in-vivo spectroscopy techniques include characterization of biomarkers following transcranial magnetic stimulation, and metabolite characterization for conditions such as addiction, pain, depression, and various forms of dementia. Collaborative studies performed at CNI include:

Method applications (DeSouza DD, Stimpson K, Baltusis L, Sacchet MD, Gu M, Hurd R, Wu H, Yeomans DC, Williams N, Spiegel D. Association between anterior cingulate neurochemical concentration and individual differences in hypnotizability. Cerebral Cortex, Volume 30, Issue 6, June 2020, Pages 3644–3654),

New method developments (Gu M, Hurd R, Noeske R, Baltusis L, Hancock R, Sacchet MD, Gotlib IH, Chin FT, Spielman DM (2018) GABA editing with macromolecule suppression using an improved MEGA-SPECIAL sequence, Magnetic Resonance in Medicine 79:41-47),

Participation in multi-site spectroscopy studies (Hui et al. Frequency drift in MR spectroscopy at 3T, NeuroImage 241(2021) 118430),

Voxel placement method development (James H. Bishop, Andrew Geoly, Naushaba Khan, Claudia Tischler, Ruben Krueger, Poorvi Keshava, Heer Amin, Laima Baltusis, Hua Wu, David Spiegel, Nolan Williams, Matthew D. Sacchet Real-Time Semi-Automated and Automated Voxel Placement using fMRI Targets for Repeated Acquisition Magnetic Resonance Spectroscopy, Journal of Neuroscience Methods 392 (2023) 109853).

Data analysis and validation methods (Hurd RE, Gu M, Okamura K, Shibata M, Ono Y, Haidar M, Riemer RK, Hanley FL, Spielman DM. Detection of elevated succinate in brain during circulatory arrest in a piglet model: A 3T 1H MR spectroscopy study. Magnetic Resonance in Medicine 93(5) 1874 (2025))

Focal 2D MRSI: a robust alternative method for metabolite measurement in challenging deep gray matter brain structures, Donna E. Murray, Meng Gu, Laima Baltusis, Hua Wu, Ralph E. Hurd, Troy A. Murray, Saché M. Coury, Daniel M. Spielman, - to be published -

1.2 Spectroscopy Literature

1.2.1 Websites

An excellent spectroscopy resource website is https://mrshub.org/ The MRSHub is a curated collection of resources for the analysis of magnetic resonance spectroscopy data. It is maintained by the Committee for MRS Code and Data Sharing of the MR Spectroscopy Study Group of the International Society for Magnetic Resonance in Medicine (ISMRM).

To analyze the data from MEGA-PRESS experiments Gannet can be used. It is a batch-analysis tool for GABA-edited MRS data. The Gannet code and instruction manual can be downloaded from here http://www.gabamrs.com/

1.2.2 Books

In Vivo NMR Spectroscopy, 2nd Edition, Author: Robin de Graaf, Wiley Online Library

The recently updated 3rd edition: In Vivo NMR Spectroscopy, 3rd Edition, Author: Robin de Graaf, Wiley Online Library

The 2014 book Magnetic Resonance Spectroscopy - Tools for Neuroscience Research and Emerging Clinical Applications

1.2.3 Papers

A very comprehensive collection of MRS papers have been published in 2021 in a special issue of NMR in Biomedicine - Advanced methodology for in vivo magnetic resonance spectroscopy - https://doi.org/10.1002/nbm.4504

Key points abstracted from the Editorial page of this special issue are summarized here and the most relevant papers to the CNI spectroscopy tools are in bold type:

"For this Special Issue, these 13 topics of advanced methodology in clinical and pre-clinical MRS have been reviewed by multi-institutional groups of authors, and a consensus overview of the most relevant facts and recommendations has been assembled for each of them. They now appear along with proffered review papers from single or smaller groups of authors and proffered research papers with a broad range of topics covering latest research results."

"The consensus articles that lay out the current state of the art and present recommendations for use in terms of several aspects of advanced MRS were written by teams of prime experts in these fields, where the teams had been instructed to self-organize under consideration of the width of the field and respecting geographic and gender aspects. However, limiting the number of authors to a size that allows productive interchange, it was not possible to include all potential expert authors as based on their publication records. Thus, it was decided for many of the papers to include a larger group of experts as a collaborator group to receive input from and to cross-check and support the experts' recommendations. None of these papers that include “experts' consensus recommendations” in their titles are to be considered as typical white papers where traditionally detailed advice on exact measurement protocols and parameters is given. This had not been our intention because the topics covered are of an advanced nature and hence inherently still touch many work-in-progress frontiers. Furthermore, all topics covered still present challenges in terms of identifying overall optimal methods as approved by the community as a whole. In contrast, the recommendations in these papers were arrived at as a consensus opinion among the specific group of experts without claiming validity for the whole community, and also with the possibility to vary the weight of advice from hints to more strongly encouraged recommendations."

"The experts' consensus papers are targeted primarily at two types of readers: on one hand, the non-MRS-specialized MR physicist or high-end user (eg a clinician or neuroscientist) commissioned with the task of implementing state-of-the-art MRS methods for a specific research or clinical target that go beyond the vendor-provided MRS techniques; on the other hand, MRS specialists who try to grasp the background and current advances in topics with which they are not intimately familiar and to provide starting points to them when they consider incorporating them in their research or technical developments."

The 13 topics for the experts' consensus recommendation papers include two general papers followed by articles on specific topics in advanced MRS grouped in three fields of research.

*Two papers on the general background of methodology and publishing in MRS.

**Terminology and concepts in MRS Kreis R, Boer V, Choi IY, et al. Terminology and concepts for the characterization of in vivo MR spectroscopy methods and MR spectra: background and experts' consensus recommendations. NMR Biomed. 2020;e4347. https://doi.org/10.1002/nbm.4347 The first article of the special issue has the broad scope of presenting the basic framework of concepts and terminology in the field of in vivo MRS, which will hopefully help to standardize the language used and thus prevent misunderstandings in future publications in the field. It also contains suggestions for the use of abbreviations and provides references to the origin of concepts, methods and common abbreviations that at times appear without reference.

**Reporting standards Lin A, Andronesi O, Bogner W, et al. Minimum reporting standards for in vivo magnetic resonance spectroscopy (MRSinMRS): experts' consensus recommendations. NMR Biomed. 2021;e4484. https://doi.org/10.1002/nbm.4484 The second paper of a more general scope is concerned with minimal reporting guidelines for papers that include MRS data, whether published in MR literature or even more so in clinical journals. It has been a common experience for many of the experienced MRS methods experts to find essential details about employed MRS methods missing from published papers or in manuscripts submitted for review. Hence, Lin et al have assembled a list of items that the authors, who are all experienced referees, suggest should be covered in the methods section of future papers including MRS results. For ease of use, the paper also contains a checklist that could be submitted along with a manuscript as supplemental material or as a way to check that all vital information is provided in the methods section.

Checklist from https://doi.org/10.1002/nbm.4484

MRI system description

a. Field strength, eg 1.5 T, 3 T, 7 T, 9.4 T

b. Manufacturer, eg General Electric, Philips, Siemens, Toshiba

c. Model, eg General Electric Signa HD/X/T/de, Optima MR450/MR450W, Discovery MR750/MR750W, Signa Premier; Siemens Biograph mMR,Magnetom, Aera, Espree, Prisma, Skyra, Trio, Verio, Magnetom 7 T, Terra; Phillips Ingenia 1.5 T S, 3 T X/S, Elition 3 T X/S, Ambition 1.5 T X/S, Achieva 1.5 T/3 T. Software version, eg Siemens VB17A, VD19, VE11C; General Electric 12x-24x; Phillips Release 5, 5.1 (R1-3), 5.6, 6

d. RF coils used (nuclei, number of channels, type, body part), eg 1H, 31P, 13C, 31P-1H; type, eg head/neck, torso, knee; if not manufacturer, design, eg butterfly, quadrature etc

e. Additional hardware, eg shim inserts, dielectric pads


Acquisition parameters in full

i. Pulse sequence, eg spin-echo, point resolved spectroscopy (PRESS), stimulated echo acquisition mode (STEAM), semi-LASER, etc.

ii. Location of volume(s) of interest (VOI(s)), eg posterior cingulate gyrus, M. tibialis anterior, internal capsule of prostate, etc. A figure that displays the VOI on anatomic images is recommended.

iii. Nominal VOI size [cm3, mm3], eg 40 × 40 × 10 mm3.

iv. Repetition time (TR), echo time (TE) [ms, s]; if STEAM, mixing time (TM).

v. Total number of excitations per spectrum.

vi. Additional sequence parameters, eg

i. Spectral width [Hz, kHz] and number of data points

ii. Frequency offset (if any)

iii. If magnetic resonance spectroscopic imaging (MRSI): specification of two-dimensional (2D) or three-dimensional (3D) spatial mapping, field of view (FOV), matrix size, acceleration factor, sampling/reconstruction method (eg parallel imaging, compressed sensing, spatial spectral encoding, etc), nominal and effective (ie final) voxel volumes, flip angles for fast MRSI

iv. For multidimensional acquisitions, number of encodings in the second spectral dimension

v. For editing methods, editing pulse information including pulse shape, bandwidth and offset frequency

vi. For multinuclear sequences: details of decoupling or polarization transfer sequences and related parameters.


f. Water suppression method (and any other suppression methods used, eg lipid suppression, outer volume suppression).

g. Shimming method, reference peak used for assessing shim performance, and thresholds for “acceptance of shim” chosen.

h. Triggering method, if used (respiratory, peripheral, cardiac triggering, including device used and delays).

i. Frequency and motion correction methods, if used (prospective or retrospective, external tracker or navigator method).


Spectral quantification methods and parameters

a. Software package used to reconstruct and analyze the MRS data including MR manufacture software (eg General Electric PROBE, Siemens Syngo, or Phillips SpectroView) and/or third-party software packages (eg LCModel, jMRUI, TARQUIN, SIVIC, INSPECTOR, FID-A, BrainSpec, MIDAS, GANNET)

b. Deviations in processing steps from quoted reference or product defaults

c. Quantitative output measures

d. Quantification references and assumptions, model fitting assumptions


Quality assurance. Studies must include the following

a. Reported variables (SNR, linewidth, and description of how they were obtained)

b. Data exclusion criteria

c. Other quality measures from fitting software are also recommended (eg standard deviation (SD), Cramér-Rao lower bound (CRLB)), and/or the robustness of the measures gained (repeatability measures if known)

d. Figure showing representative spectra


*Four papers dealing with commonly used MRS acquisition sequences and processing methods.

**Advanced single-voxel MRS Oz G, Deelchand DK, Wijnen JP, et al. Advanced single voxel 1H magnetic resonance spectroscopy techniques in humans: experts' consensus recommendations. NMR Biomed. 2020;e4236. https://doi.org/10.1002/nbm.4236

**Advanced neuro-MRSI Maudsley AA, Andronesi OC, Barker PB, et al. Advanced magnetic resonance spectroscopic neuroimaging: experts' consensus recommendations. NMR Biomed. 2020;e4309. https://doi.org/10.1002/nbm.4309

**Spectral editing Choi IY, Andronesi OC, Barker P, et al. Spectral editing in 1H magnetic resonance spectroscopy: experts' consensus recommendations. NMR Biomed. 2020;e4411. https://doi.org/10.1002/nbm.4411

**Processing and quantification Near J, Harris AD, Juchem C, et al. Preprocessing, analysis and quantification in single-voxel magnetic resonance spectroscopy: experts' consensus recommendations. NMR Biomed. 2020;e4257. https://doi.org/10.1002/nbm.4257


  • Three papers related to MRS techniques that are critical to ensure the quality of data.
    • Water and lipid suppression Tkac I, Deelchand D, Dreher W, et al. Water and lipid suppression techniques for advanced 1H MRS and MRSI of the human brain: experts' consensus recommendations. NMR Biomed. 2020;e4459. https://doi.org/10.1002/nbm.4459
    • B0 shimming Juchem C, Cudalbu C, de Graaf RA, et al. B0 shimming for in vivo magnetic resonance spectroscopy: experts' consensus recommendations. NMR Biomed. 2020;e4350. https://doi.org/10.1002/nbm.4350
    • Motion correction Andronesi OC, Bhattacharyya PK, Bogner W, et al. Motion correction methods for MRS: experts' consensus recommendations. NMR Biomed. 2020;e4364. https://doi.org/10.1002/nbm.4364


  • Four papers appertaining to special targets of MRS studies.
    • Macromolecular signals and ways to accommodate them in1H MR brain spectra Cudalbu C, Behar KL, Bhattacharyya PK, et al. Contribution of macromolecules to brain 1H MR spectra: experts' consensus recommendations. NMR Biomed. 2020;e4393. https://doi.org/10.1002/nbm.4393
    • 1H MRS of skeletal muscle Krssak M, Lindeboom L, Schrauwen-Hinderling V, et al. Proton magnetic resonance spectroscopy in skeletal muscle: experts' consensus recommendations. NMR Biomed. 2020;e4266. https://doi.org/10.1002/nbm.4266
    • 31P MRS of skeletal muscle Meyerspeer M, Boesch C, Cameron D, et al. 31P magnetic resonance spectroscopy in skeletal muscle: experts' consensus recommendations. NMR Biomed. 2020;e4246. https://doi.org/10.1002/nbm.4246
    • Specifics for MRS methods in preclinical applications Lanz B, Abaei A, Braissant O, et al. Magnetic resonance spectroscopy in the rodent brain: experts' consensus recommendations. NMR Biomed. 2020;e4325. https://doi.org/10.1002/nbm.4325


  • This special issue also includes authoritative reviews of the current state of
    • fast MRSI methodology Bogner W, Otazo R, Henning A. Accelerated MR spectroscopic imaging—a review of current and emerging techniques. NMR Biomed. 2020;e4314. https://doi.org/10.1002/nbm.4314
    • hyperpolarized 13C MRI and MRS Crane JC, Gordon JW, Chen H-Y, et al. Hyperpolarized 13C MRI data acquisition and analysis in prostate and brain at University of California, San Francisco. NMR Biomed. 2020;e4280. https://doi.org/10.1002/nbm.4280


  • Fifteen proferred original research contributions complete this special issue. They cover latest research results in terms of novel advanced MRS methodology or its application. The methodology addresses issues in

**standardization - Deelchand DK, Berrington A, Noeske R, et al. Across-vendor standardization of semi-LASER for single-voxel MRS at 3T. NMR Biomed. 2019;e4218. https://doi.org/10.1002/nbm.4218

    • diffusion MRS Lundell H, Ingo C, Dyrby TB, Ronen I. Cytosolic diffusivity and microscopic anisotropy of N-acetyl aspartate in human white matter with diffusion-weighted MRS at 7 T. NMR Biomed. 2020;e4304. https://doi.org/10.1002/nbm.4304 Hanstock C, Beaulieu C. Rapid acquisition diffusion MR spectroscopy of metabolites in human brain. NMR Biomed. 2020;e4270. https://doi.org/10.1002/nbm.4270 Genovese G, Marjańska M, Auerbach EJ, et al. In vivo diffusion-weighted MRS using semi-LASER in the human brain at 3 T: methodological aspects and clinical feasibility. NMR Biomed. 2020;e4206. https://doi.org/10.1002/nbm.4206
    • editing Deelchand DK, Marjańska M, Henry P-G, Terpstra M. MEGA-PRESS of GABA+: influences of acquisition parameters. NMR Biomed. 2019;e4199. https://doi.org/10.1002/nbm.4199 Ma RE, Murdoch JB, Bogner W, Andronesi O, Dydak U. Atlas-based GABA mapping with 3D MEGA-MRSI: cross-correlation to single-voxel MRS. NMR Biomed. 2020;e4275. https://doi.org/10.1002/nbm.4275 Bell T, Boudes ES, Loo RS, et al. In vivo Glx and Glu measurements from GABA-edited MRS at 3 T. NMR Biomed. 2020;e4245. https://doi.org/10.1002/nbm.4245
    • novel acquisition techniques Kulpanovich A, Tal A. What is the optimal schedule for multiparametric MRS? A magnetic resonance fingerprinting perspective. NMR Biomed. 2019;e4196. https://doi.org/10.1002/nbm.4196 Posse S, Sa De La Rocque Guimaraes B, Hutchins-Delgado T, et al. On the acquisition of the water signal during water suppression: high-speed MR spectroscopic imaging with water referencing and concurrent functional MRI. NMR Biomed. 2020;e4261. https://doi.org/10.1002/nbm.4261
    • processing techniques Francischello R, Geppi M, Flori A, Vasini EM, Sykora S, Menichetti L. Application of low-rank approximation using truncated singular value decomposition for noise reduction in hyperpolarized 13C NMR spectroscopy. NMR Biomed. 2020;e4285. https://doi.org/10.1002/nbm.4285 Marjańska M, Terpstra M. Influence of fitting approaches in LCModel on MRS quantification focusing on age-specific macromolecules and the spline baseline. NMR Biomed. 2019;e4197. https://doi.org/10.1002/nbm.4197 Landheer K, Swanberg KM, Juchem C. Magnetic resonance Spectrum simulator (MARSS), a novel software package for fast and computationally efficient basis set simulation. NMR Biomed. 2019;e4129. https://doi.org/10.1002/nbm.4129
    • reported applications probe the feasibility of novel uses of advanced MRS methods van Houtum Q, Mohamed Hoesein FAA, Verhoeff JJC, et al. Feasibility of 31P spectroscopic imaging at 7 T in lung carcinoma patients. NMR Biomed. 2019;e4204. https://doi.org/10.1002/nbm.4204 Rioux JA, Hewlett M, Davis C, et al. Mapping of fatty acid composition with free-breathing MR spectroscopic imaging and compressed sensing. NMR Biomed. 2019;e4241. https://doi.org/10.1002/nbm.4241 Peeters TH, van Uden MJ, Rijpma A, Scheenen TWJ, Heerschap A. 3D 31P MR spectroscopic imaging of the human brain at 3 T with a 31P receive array: an assessment of 1H decoupling, T1 relaxation times, 1H-31P nuclear Overhauser effects and NAD+. NMR Biomed. 2019;e4169. https://doi.org/10.1002/nbm.4169



Several new publications here on advanced editing techniques - http://www.gabamrs.com/


Voxel placement publication

AutoVOI: real‐time automatic prescription of volume‐of‐interest for single voxel spectroscopy Young Woo Park Dinesh K. Deelchand James M. Joers Brian Hanna Adam Berrington Joseph S. Gillen Kejal Kantarci Brian J.Soher Peter B. Barker HyunWook Park Gülin Öz Christophe Lenglet Magn Reson MEd. 2018;80:1787-1798 https://doi.org/10.1002/mrm.27203


New open-source processing package currently under evaluation -

Osprey: Open-source processing, reconstruction & estimation of magnetic resonance spectroscopy data Georg Oeltzschner Helge J.Zöllner Steve C.N.Hui Mark Mikkelsen Muhammad G.Saleh Sofie Tapper Richard A.E. Edden Journal of Neuroscience Methods Volume 343, 1 September 2020, 108827 https://doi.org/10.1016/j.jneumeth.2020.108827


Presentation at 2020 ENC Meeting - Accelerated MR spectroscopic imaging—a review of current and emerging techniques

Accelerated MR spectroscopic imaging—a review of current and emerging techniques Wolfgang Bogner Ricardo Otazo Anke Henning NMR in Biomedicine.2020;e4314 https://doi.org/10.1002/nbm.4314

1.3 Spectroscopy Data Acquisition Methods at CNI

1.3.1 Current CNI spectroscopy sequences

For all spectroscopy research projects CNI actively follows the recommended best practices from the ISMRM (International Society for Magnetic Resonance in Medicine) Spectroscopy Study Group and recently published experts’ consensus recommendations (1,2,3,4,5,6) . Currently the semi-LASER sequence is the ISMRM consensus method, particularly for multi-site 3T MRS studies(5). We have, therefore, transitioned studies at CNI from previously recommended sequences (PRESS, as example) to the sLASER sequence (a GE product sequence) for both short TE single voxel and new focal 2D MRSI studies.

[1] Choi I., Kreis R. Advanced methodology for in vivo magnetic resonance spectroscopy, NMR in Biomedicine, 2021;34:e4504

[2] Wilson M, Andronesi O, Barker PB, et al. Methodological consensus on clinical proton MRS of the brain: review and recommendations. Magn Reson Med. 2019;82:527-550

[3] Maudsley AA, Andronesi OC, Barker PB, et al. Advanced magnetic resonance spectroscopic neuroimaging: experts' consensus recommendations. NMR Biomed. 2021;34:e4309

[4] Oz G, Deelchand DK, Wijnen JP, et al. Advanced single voxel 1H magnetic resonance spectroscopy techniques in humans: experts' consensus recommendations. NMR Biomed. 2021;34:e4236

[5] Deelchand DK, Berrington A, Noeske R, et al. Across-vendor standardization of semi-LASER for single-voxel MRS at 3T. NMR Biomed. 2021;34:e4218.

[6] Near J, Harris AD, Juchem C, et al. Preprocessing, analysis and quantification in single-voxel magnetic resonance spectroscopy: experts' consensus recommendations. NMR Biomed. 2021;34:e4257.

1.3.2 sLaser prototocol examples on CNI scanner for single voxel spectroscopy (SVS) and focal MR spectroscopic imaging (focal-MRSI)

An example spectroscopy protocol (CNI-spectro-2025) is located in the CNI "Other" tab on the CNI 3T UHP scanner with examples of the sLaser sequence for both single voxel and 2D focal MRSI applications. The table of the typical sequences and accompanying screen shots is shown below.



Spectroscopy Sequence Description and General Information
Localizer
T1 High Resolution T1 with automatic reformatting for sagittal, coronal, and axial views for voxel placement.
HOS (High Order Shimming) The high order shimming sequence is performed prior to 2D MRSI data collection to improve spectral data quality. The GE works in progress (WIP) experimental patch incorporates an improved ratio of matrix size to spatial coverage
Voxel Placement Sequence for rotated voxel placement (details described in separate section further below)
sLASER This sequence is now a GE product sequence (PROBE-sl) and is consistent with the ISMRM Experts' consensus recommendations for this sequence. MRS and MRSI at 3T or higher have technical challenges such as achieving a uniform B1 field or a specific flip angle. The use of the semi-localized by adiabatic selective refocusing (sLASER) sequence can address these issues. The major advantage of the sLASER approach is reduced chemical shift displacement error. This is especially important for volume excited MRSI, avoiding spatial regions with biased metabolite ratios and J-evolution differences.

1.3.3 Screen shots of parameters and CV's for a typical spectroscopy protocol

1.3.3.1 T1

Anatomical Scan Parameters: A T1-weighted structural scan was acquired using a 3D fast gradient-echo (GRE) BRAin VOlume (BRAVO) sequence: TE = 3.2 ms, TR = 7.83 ms, field of view = 256 × 256 mm, voxel size = 1 x 1 x 1 mm, number of slices = 172, slice orientation = sagittal, FA = 11 deg, receiver bandwidth = 27.78 kHz, acquisition time = 4 min and 4 sec. The Single voxel (SVS) and MRSI Volumes of Interest were prescribed on the T1-weighted scans.


1.3.3.2 Single Voxel

An example of single voxel of the ACC region

After reformatting the T1 images to obtain high resolution images in the coronal, sagittal, and axial views, placing a voxel on the axial image will allow for voxel size adjustment in the details tab in the "length" parameters (example of 16 X 20 X 20 shown in Figures below). Key parameters used in the sLaser sequence are outlined in the table below and referenced to figures 1-4 further below following parameter reporting guidance - Lin A, Andronesi O, Bogner W, et al. Minimum reporting standards for in vivo magnetic resonance spectroscopy (MRSinMRS): experts' consensus recommendations.


Figure 1. sLASER voxel prescription with coronal, sagital and axial reference views

Figure 2. Click on the right arrow to reveal details tab showing additional information including TE and NEX

Figure 3. Selection of the Advanced tab to reveal advanced control water suppression and spectral sampling conditions

Advanced tab coronal and sagittal views only (Figure 4)

1.3.3.3 2D MRSI

Example of Right Subcortical MRSI

After reformatting the T1 images to obtain high resolution images in the coronal, sagittal, and axial views, placing an MRSI slab on the axial image will allow for size adjustment in the details tab in the "length" parameters and is done prior to changing the sequence from a single voxel acquisition mode to the MRSI acquisition mode. Key parameters used in the sLaser sequence are outlined in the table below and referenced to figures 5-8 further below following parameter reporting guidance - Lin A, Andronesi O, Bogner W, et al. Minimum reporting standards for in vivo magnetic resonance spectroscopy (MRSinMRS): experts' consensus recommendations.



Details tab with coronal, sagittal, and axial views (Figure 5)

Details tab with coronal and sagittal views only (Figure 6)

Advanced tab coronal and sagittal views only (Figure 7)

Advanced tab coronal and sagittal views only (Figure 8)

1.4 Tools for Spectroscopy Data Acquisitions

1.4.1 High Order Shimming for MRSI

High Order Shimming (HOS): A General Electric (GE) higher order shimming sequence of the VOI box was performed prior to 2D MRSI data collection to improve spectral data quality. The GE works in progress (WIP) experimental patch incorporates an improved ratio of matrix size to spatial coverage, 64 x 64 matrix to 128 x 128 matrix.

Shimming - Placement of MRSI Volume of Interest on T1 images followed by standard shimming workflow procedures in the following figures

Shimming-1

Shimming-2

Shimming-3

Shimming-4

Shimming-5

Shimming-6

1.4.2 Prescribing a rotated voxel

At the moment GE’s DV26 and higher software platforms release doesn’t support voxel rotation for spectroscopy sequences. A workaround however is available:

(1) After the 3-plane reconstruction of the T1w images, setup a 3D imaging scan. We saved a template of this 3D scan in the protocol “CNI Example Spectroscopy” and named it as “Voxel prescription”. Add this sequence to your protocol and put it before the MRS scan.

(2) Setup the voxel prescription scan. The Scan Plane is set to “Oblique”, FOV and Locs per Slab are set as close to the voxel size of the spectro scan as possible. Prescribe the 3D box, place it to the desired location and rotate to the right angle. Because the box is usually bigger than the voxel size you want to prescribe, the coverage you see in this step is not accurate. It’s crucial to get the correct orientation of the box. Save Rx.

(3) Setup the MRS scan. Copy Rx from the voxel prescription scan. By default the Mode Filter in the Copy Rx is set to “MRS”, you need to change it to “All” or “3D” in order to see the voxel prescription scan in the Copy Rx list. Select it and accept.

(4) Adjust voxel location and size. You can move the box around and change its size on the graphic interface, or set its coordinates and size by setting the Center and Length in X, Y, Z. If you want to adjust the orientation of the voxel, you need to go back to the 3D voxel prescription scan, and repeat step 2-4 again. After you finish setting up the MRS scan, Save Rx and proceed with scanning.

1.4.3 Extracting voxel prescription information retrospectively

The prescription information of the voxel of an MRS scan is saved in the header of the raw data (p-file). Specifically, the x, y, z dimensions of the voxel are stored in header fields rdb_hdr_image.user8, rdb_hdr_image.user9, rdb_hdr_image.user10; the x, y, z locations of the center of the voxel are stored in header fields rdb_hdr_image.user11, rdb_hdr_image.user12, rdb_hdr_image.user13, in RAS coordinates (e.g. if the voxel is at L26.0 then rdb_hdr_image.user11 will record -26.0). The unit is mm.

To look for this information on Flywheel, open the information window of the p-file, and search for op_user_8, op_user_9, op_user_10, etc.

1.5 Processing of sLASER SVS and MRSI data

Specific customized steps to process the 2D focal MRSI data were developed and are shown with a listing of additional data processing details below. An analogous custom data processing pipeline is used for single voxel data processing.




2D focal MRSI sLASER Data Processing and Reconstruction: To suppress leakage of the artifact signals from voxels outside of the excited volume, a 2D version of the spatial Fermi filter was applied to the k-space data before Fourier transformation. Coil combination was then performed voxel by voxel using a summed square of the magnitude of the first data point in the FID. The spectral grid was extrapolated to 32 x 32 grid.

3D T1 weighted Processing: Structural data were processed with the open source package FreeSurfer tool(36) version 7.3.2 for automated whole brain tissue segmentation of Gray Matter (GM) and White Matter (WM) as well as Cerebrospinal Fluid (CSF). Using X atlas, brain regions from the 3D T1 weighted image are parcellated, masked and labeled. Visual quality control procedures were performed including assessing motion artifacts, checking segmentation accuracy and confirming there were no processing errors.

MRSI Mask: An in-house MATLAB script created a multi-value (non-binary) mask of the MRSI Volume of Interest that was registered to the 3D T1 weighted MRI anatomical scan. The location of the MRSI mask and regions within the mask were quality checked for accuracy against screenshots of the MRSI Volume of Interest taken during data acquisition.

Gray Matter/ White Matter/ Cerebrospinal Fluid (GM/WM/CSF) Segmentation (Separate GM/WM/CSF): After the 3D T1w structural processing and MRSI Mask steps are completed, the outputs from these steps are fed into two in-house data processing scripts in order to compute and separate voxels based on tissue percentages of GM/WM/CSF for each voxel in the Volume of Interest and to identify (label) brain regions in the MRSI Mask (achieved with two in-house data processing scripts). This was done to identify and correct for potential influences on metabolite estimates from different tissue amounts in each voxel using percentage of gray matter as a covariant (GM/(GM+WM)).

1.6 Legacy and Other Spectroscopy Sequences

Legacy and other spectroscopy sequences used at CNI include methods both for edited GABA (gamma-Aminobutyric acid) specific data acquisition (MEGA-PRESS [1] and IM-SPECIAL [3]), and for multi-metabolite data acquisition (Optimized-PRESS [4], [5], [6]). Many sequences are linked to automatic processing pipelines in CNI's data management system, Flywheel, as referenced in the table below.


Spectroscopy Sequence Measured Metabolites Analysis Methods
MEGA-PRESS [1] GABA+, Glx(Glutamate, Glutmine) Gannet [2]
IM-SPECIAL [3] GABA, Glu(Glutamate), Glx(Glutamate, Glutamine) Sequence specific Matlab code
Optimized-PRESS [4], [5], [6] All metabolites LCModel fitting [7]


References

[1] Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R (1998) Simultaneous in vivo spectral editing and water suppression, NMR Biomed. 11:266–272 https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291099-1492%28199810%2911%3A6%3C266%3A%3AAID-NBM530%3E3.0.CO%3B2-J

[2] Richard A.E. Edden, Nicolaas A.J. Puts, Ashley D. Harris, Peter B. Barker, and C. John Evans (2014) Gannet: A Batch-Processing Tool for the Quantitative Analysis of Gamma-Aminobutyric Acid–Edited MR Spectroscopy Spectra, Journal of Magnetic Resonance Imaging 40:1445–1452 https://doi.org/10.1002/jmri.24478

[3] Gu M, Hurd R, Noeske R, Baltusis L, Hancock R, Sacchet MD, Gotlib IH, Chin FT, Spielman DM (2018) GABA editing with macromolecule suppression using an improved MEGA-SPECIAL sequence, Magnetic Resonance in Medicine 79:41-47 https://doi.org/10.1002/mrm.26691

[4] Webb PG, Sailasuta N, Kohler SJ, Raidy T, Moats RA, Hurd R (1994) Automated single voxel proton MRS: technical development and multisite verification, Magnetic Resonance in Medicine 31(4):365-373 https://doi.org/10.1002/mrm.1910310404

[5] Bodenhausen G, Freeman R, Turner DL (1977) Suppression of artifacts in two dimensional J spectroscopy, Journal of Magnetic Resonance Imaging 27:511-514 https://doi.org/10.1016/0022-2364(77)90016-6

[6] Tran TK, Vigneron DB, Sailasuta N, Tropp J, Le Roux P, Kurhanewicz J, Nelson S, Hurd R (2000) Very selective suppression pulses for clinical MRSI studies of brain and prostate cancer, Magnetic Resonance in Medicine 43(1):23-33. https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291522-2594%28200001%2943%3A1%3C23%3A%3AAID-MRM4%3E3.0.CO%3B2-E

[7] Provencher SW (2001) Automatic quantitation of localized in vivo1H spectra with LCModel, NMR in Biomedicine 14(4):260-264 https://doi.org/10.1002/nbm.698

1.7 Spectroscopy Data Processing Tools at CNI for legacy sequences

CNI currently uses Flywheel as its data base management system. A critical feature of this data base management is the ability to share computational methods within the system. The CNI now provides a combination of data repository and integrated open source processing tools such as Gannet [2] and LCModel [7]. This combination of tools supports scientific transparency for both data and computational sharing. Spectroscopy analysis methods such as LCModel can be containerized as a gear in Flywheel for automated processing and data visualization.


Flywheel


Each of the spectroscopy sequences is linked to a Flywheel gear for automatic data processing

Spectroscopy Sequence Measured Metabolites Analysis Methods
Optimmized_PRESS All metabolites Sequence specific Matlab code, LCModel fitting - Flywheel processing gear placeholder information here: LCMODEL_r_dlpfc_nfl_[BASIS_SET=02_01_19,FIXED_NAA=0]_(2021-05-13)

For users using the CNI Optimized PRESS "nfl" sequence with LCModel data analysis - Users who are in groups that are not themselves Flywheel "Lab" customers will need to download their results from the session tab now (not the analyses tab as was done before and shown in the figure below)

If you are using Google Chrome as the browser to download the processed data, then you will need to add the extension .zip to the downloaded file name. This operation does not not need to be done if using Safari or Firefox browsers.

MEGA-PRESS results will continue to be in the analyses tab.


LCModel Results



Spectroscopy Sequence Measured Metabolites Analysis Methods
MEGA-PRESS GABA+, Glx(Glutamate, Glutmine) To analyze the data from MEGA-PRESS experiments, we recommend Gannet, a batch-analysis tool for GABA-edited MRS data http://www.gabamrs.com/. Currently the latest version 3.1 is Docker containerized. This needs to be manually run, but this analysis method will soon be changed to a Flywheel gear for automatic analysis and storage of results (see location of data analysis results section below).

References from the Gannet web site include:

Richard A.E. Edden, Nicolaas A.J. Puts, Ashley D. Harris, Peter B. Barker, and C. John Evans (2014) Gannet: A Batch-Processing Tool for the Quantitative Analysis of Gamma-Aminobutyric Acid–Edited MR Spectroscopy Spectra, Journal of Magnetic Resonance Imaging 40:1445–1452 https://doi.org/10.1002/jmri.24478

Paul G.Mullins David J.McGonigle Ruth L.O'Gorman Nicolaas A.J.Puts RishmaVidyasagar C. JohnEvans Cardiff Symposium on MRS of GABA Richard A.E.Edden Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA https://doi.org/10.1016/j.neuroimage.2012.12.004

Ashley D. Harris, Muhammad G. Saleh, Richard A.E. Edden Edited 1H magnetic resonance spectroscopy in vivo: Methods and metabolites https://doi.org/10.1002/mrm.26619

The Gannet manual can be downloaded here - http://www.gabamrs.com/downloads

An example of the use of voxel segmentation is described here - DeSouza DD, Stimpson K, Baltusis L, Sacchet MD, Gu M, Hurd R, Wu H, Yeomans DC, Williams N, Spiegel D. Association between anterior cingulate neurochemical concentration and individual differences in hypnotizability. Cerebral Cortex, Volume 30, Issue 6, June 2020, Pages 3644–3654, https://doi.org/10.1093/cercor/bhz332,

Analysis results of MEGA-PRESS with Gannet is shown in Figure 1 (Gannet Fit), Figure 2 (Gannet Output), Figure 3 (Gannet CoRegister), and Figure 4 (Gannet Segment) for the ACC brain region.

Gannet Figure 1
Gannet Figure 2
Gannet Figure 3
Gannet Figure 4

2. Miscellaneous Historical Information

Historical Information

Retrieved from "http://cni.su.domains/wiki/index.php?title=Spectro&oldid=59525"