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Cross-validated full-field of view MRSI using a new spatial lipid extraction technique and HSVD and PG algorithms in the human brain.
Peter Adany1, In-Young Choi1,2,3, and Phil Lee1,3

1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, 2Neurology, University of Kansas Medical Center, Kansas City, KS, United States, 3Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Synopsis

Reliable 1H MRS measurement in the brain is challenging due to strong lipid signals as high as two orders of magnitude stronger than metabolites. We propose a new spatial-domain post processing technique to extract the lipid signal and compare our method with the HSVD and PG algorithms applied to full field of view (FOV) MRSI data (no lipid nulling, no outer volume suppression). Results of lipid removal were assessed visually and by spectral quantification of MRSI voxels for N=9 subjects. Our method outperformed HSVD and PG and achieved reliable full-FOV MRSI, promising to reach the maximum potential of whole-brain MRSI.

Target Audience

Scientists and technologists interested in advanced in vivo 1H MRS methods to measure neurochemicals in the whole brain to enable region-specific quantitative analysis of metabolic activity.

Introduction

Subcutaneous lipids pose a major obstacle in MRSI of the brain due to their high concentrations (over 100× those of metabolites), broad spectral linewidth (short T2*) and phase distortions resulting from poor shimming in the extracranial regions, and the broad point spread function (PSF) of MRSI. Inversion recovery (IR) nulling and outer volume suppression (OVS) have been necessary to suppress extracranial lipids in MRSI to achieve accurate quantification of neurochemicals. Recently, lipid removal has been achieved through post processing by taking advantage of high resolution imaging or chemical shift spectral prior information to model the lipid signal components [1-8]. We have developed a spatial post-processing reconstruction method, dubbed Fast Lipid Pattern Estimation and Removal (FLIPPER), with minimal complexity and computational demand compared to previous approaches, that enables quantification of all MRSI voxels over the brain from full-field of view (FOV) MRSI. The purpose of this study was to examine the performance of our proposed method in vivo and compare it with the well-known spectral HSVD [9] and spatial Papoulis-Gerchberg (PG) [10] algorithms.

Theory

A complex-valued image of k-space data can be defined as $$ p_R (x,y)=1/N\sum_{n=1}^Ns_n e^{j2\pi (k_{n_x} x+k_{n_y} y)} {}{}(1)$$ where $$$ k_{n_x},k_{n_y} $$$ are the elements of phase encoding vectors $$$k_n$$$, and $$$x,y$$$ are spatial coordinates corresponding to a zero-padded uniform k-space. In this view, the lipid signal components of $$$ \textbf{s} $$$ produce ringing artifacts associated with the point spread function (PSF). Conversely, the contribution to $$$ \textbf{s} $$$ by an image $$$ c(x,y) $$$ with unrestricted k-space is given by $$s_n=\sum_{m=1}^M c(x_m,y_m) e^{-j2\pi(k_{n_x}x_m+k_{n_y}y_m)} (2)$$where $$$ x_m,y_m $$$ are the image coordinates. This can be expressed by a matrix relation $$ \textbf{s}=G\textbf{c} (3)$$ In MRSI, $$$ \textbf{s} $$$ contains lipid (extracranial) and metabolite (intracranial) contributions $$$ \textbf{s}=\textbf{s}_l+\textbf{s}_m $$$. The error of a fit to $$$ \textbf{s}$$$ can be minimized in the least squares (LS) sense including a regularization parameter, $$ \underset{c}{\operatorname{arg min}} ||\textbf{s}-G\textbf{c}||^2 + \lambda||R\textbf{c}||^2 (4)$$ The key to improving the performance of Eq. 4 is to tailor the basis functions to address signal leakage between isolated domains in tandem with the regularized inverse. We propose a simple, physical rationale to set up and solve the problem of Eq. 3. Finally, we subtract the reconstructed lipid signal from original MRSI data prior to lineshape fitting based quantitation.

Methods

All subjects were consented according to institutional review board approved protocols. All MR measurements were perfomed on a 3 T scanner (Skyra, Siemens) using a 32 channel head receive coil. MRSI data were acquired using a semi-LASER [11] sequence with frequency drift correction using an interleaved reference [12] (TE/TR=35/1600ms, matrix=16×16, FOV=20cm), with the slab positioned across the prefrontal to parietal lobes. High resolution imaging was performed using a sagittal MPRAGE sequence with 176×256×256 dimensions. Subcutaneous lipid segmentation was performed by in-house routines (Matlab, Natick, MA) on image slices resampled to 128×128. The extracranial lipid signal was isolated from raw MRSI data using the theory described above, before coil combination. The HSVD and PG algorithms were implemented as previously desribed [9, 10, 13], with the HSVD poles residing away from metabolites of interest, i.e., <1.9 ppm, and number of poles for optimal removal and support size that yielded satisfactory results with reasonable computation time. For the PG algorithm, 15 iterations were applied using the same lipid mask. Spectral quantification was performed on lipid-subtracted data after coil summation using LCModel [14] on all MRSI voxels with ≥50% tissue fraction.

Results and Discussion

Our proposed method could isolate and remove the large nuisance lipid signals originating from the scalp in full-FOV MRSI (Fig. 1) without a loss of neurochemical signals originated from the brain (Fig. 2). The lipid removal was consistent in all nine subjects for both voxels located in the middle and at the edge of the brain (Fig. 3). Lipid removal performance of the proposed method was superior to that of the spectral HSVD and PG algorithm as indicated by the higher number of voxels that could pass spectral quality criteria and smaller variance of quantified neurochemical concentrations (Fig. 4). In conclusion, we have demonstrated a successful removal of interfering lipid signals from MRSI data acquired without any lipid attenuating strategies using a new lipid removal algorithm. The proposed algorithm could be readily extended to 3-dimensional MRSI data sets and is promising approach to extend neurochemical measurement to the previously inaccessible functionally important area, e.g., outer cortical areas.

Acknowledgements

The Hoglund Brain Imaging Center is supported by the NIH (S10RR029577) and the Hoglund Family Foundation.

References

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[8] Q. Ning, C. Ma, F. Lam, and Z. P. Liang, “Spectral Quantification for High-Resolution MR Spectroscopic Imaging with Spatiospectral Constraints,” IEEE Trans Biomed Eng, Jul 27, 2016.

[9] H. Barkhuijsen, R. Debeer, and D. Vanormondt, “Improved Algorithm for Noniterative Time-Domain Model-Fitting to Exponentially Damped Magnetic-Resonance Signals,” Journal of Magnetic Resonance, vol. 73, no. 3, pp. 553-557, Jul, 1987.

[10] A. Papoulis, “New Algorithm in Spectral Analysis and Band-Limited Extrapolation,” Ieee Transactions on Circuits and Systems, vol. 22, no. 9, pp. 735-742, 1975.

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Figures

Figure 1. Spectra from full FOV 2D MRSI acquired without lipid suppression before (A) and after subtracting the lipid signal component, which was isolated from the raw MRSI data using the proposed method (B). Spectra in shown in (B) were 25x magnified compared with dose in (A).

Figure 2. Spectra from a central voxel for one subject, showing the original raw spectrum (shown in blue), lipid signal reconstructed from the raw data using the proposed FLIPPER method (shown in red), and the resulting spectrum after subtracting the lipid from the raw data (shown in black, magnified 10x). Inset image shows the MRI from center of the slab, with the voxel location indicated (shown light blue).

Figure 3. Spectra after lipid signal removal using the proposed method for 9 human subjects. For each subject a spectrum is shown from the center of the brain (column A) and adjacent to the scalp (column B). The excellent performance of the proposed lipid removal algorithm is shown by the quality of spectra with nearly no residual lipid signals.

Figure 4. Comparison of three methods (proposed FLIPPER method, HSVD algorithm and PGA) is shown in (A) with group average (N=9) of relative total N-acetylaspartate (tNAA/Cr), total choline (tCho/Cr) and glutamate and glutamine (Glx/Cr). Concentrations were normalized to the mean across subjects. Metabolite map images of tNAA/Cr, tCho/Cr and tGlx/Cr are shown for one subject for each of the tested methods (FLIPPER, HSVD and PGA). FLIPPER yielded 62% of input voxels with tNAA/Cr Cramer Rao lower bound (%SD) ≤ 5, while HSVD yielded 44% and PGA yielded 57%, indicating more reliable performance by the proposed FLIPPER algorithm.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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