Manoj Kumar Sarma1, Andres Saucedo1, Uzay E. Emir2, and M. Albert Thomas1
1Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States, 2School of Health Sciences, Purdue University – West Lafayette, West Lafayette, IL, United States
Synopsis
We implemented a semi-LASER localized total
correlated spectroscopic imaging (EP-TOCSI) sequence on a 3T MRI scanner. Compared to L-COSY the coherence transfer 900
RF pulse was replaced by a spin-lock module consisting of adiabatic train of RF
pulses using MLEV4 phase cycling; also, multi-voxel encoding included EPI read-out
combined with phase-encoding. After evaluating the performance of the 4D
EP-TOCSI sequence using a corn oil phantom, we investigated calf muscle of 2
healthy and 1 type 2 diabetic subjects.
There were relayed cross peaks in addition to COSY cross peaks conventionally
recorded by L-COSY or EP-COSI.
Introduction:
Echo-planar correlated spectroscopic imaging (EP-COSI)1,
which combines L-COSY2 with an echo-planar3 readout combined
with phase-encoding gradients for correlated SI,
facilitates improved
detection of overlapping metabolites with increased
spectral dispersion from multiple spatial regions.
In skeletal muscle, EP-COSI has been used to differentiate
saturated and unsaturated lipid components, allowing estimation of the degree
of unsaturation4,5,6. Based on the same principle of COSY, total
correlated spectroscopy (TOCSY)7 is another powerful technique that contains information about the directly
scalar coupled spins coherence transfer. However, TOCSY can provide additional cross
peaks for nuclei that are connected by a long chain of coupling and exhibits an in-phase magnetization
transfer. This can be valuable, as in
some cases metabolites might have pairs of neighboring spins with similar
chemical shifts. In-vivo 1D spectral-editing TOCSY has been tried
previously with both adiabatic8,9 and non-adiabatic mixing10.
Different localized 2D version of TOCSY11,12 has been proposed and
implemented in human brain. However, due to the complex nature of the sequence
potential of TOCSY has not been fully exploited in-vivo as SAR associated with
the requirement of a sustained train of RF pulses during TOCSY mixing remains
the main issue. Here, we propose a novel version of localized 4D echo planar total
correlated spectroscopic imaging
(EP-TOCSI) and implemented in human calf muscle in-vivo at 3T. We used a short TE semi-LASER (sLASER) localization
and introduce a novel mixing module containing multiple adiabatic
B1-insensitive refocusing (BIREF-1) pulses13. We
hypothesize that the proposed technique will detect relayed COSY resonances in human calf muscle.Materials and Methods:
Fig.1 shows the
schematic diagram of the EP-TOCSI sequence with sLASER localization. The
spin-lock (SL) mixing module consists of train of four adiabatic BIREF pulses (duration
of 6ms) with adiabatic half passage (AHP) tip-up/down pulses. The phases of
the BIREF-1 pulses were prescribed according to MLEV-4 scheme14. TOCSY block does not contribute to the TE and total TE
is nothing but the TE of the sLASER block. The time between the last AFP and
the TOCSI block was incremented to introduce the t1 evolution.
Global water suppression was performed using a WET15 scheme.
To
test the sequence, corn oil phantom data was acquired first. The sequence was further evaluated in the calf
muscle of two healthy volunteers (age 37.5±6.4years) and one type 2 diabetic
patients (T2DM) (65years). All data were collected on a 3T Prisma MRI
scanner using a 15 channel knee ‘transmit/receive’ coil. The following
parameters were used for acquiring the 4D EP-TOCSI data: TR/TE = 2s/29ms, voxel
resolution=3.37cm3, 64 Δt1
increments, 512 bipolar echo pair, FOV= 24x24cm2, F1 and F2
bandwidths of 1250 Hz and 1190 Hz respectively. A non-water-suppressed scan
with t1=1 was also recorded for eddy current correction and coil
combination. For comparison, sLASER COSI with were also acquired with similar
parameters as TOCSI, except TE=34 ms. Acquired data were extracted,
reconstructed and post-processed16 with a library of custom
MATLAB-based program.Results:
Fig. 2 shows our initial results in corn
phantom showing extracted spectra recorded with sLASER EP-COSI and
EP-TOCSI. Cross peaks of all lipid
multiplets were well visible and separated from the main diagonal. Due to
coherent transfer of in-phase magnetization in TOCSI the multiplet structure of
each cross peak is more clearly apparent. Relayed cross peaks of
intramyocellular (IMCL)/extramyocellular lipids (EMCL) are visible in TOCSI
spectra which cannot be detected in EP-COSI. In vivo human calf muscle spectra from EP-TOCSI acquired in a
65 years-old T2DM patient can be seen in Fig. 3 from the bone marrow (b),
tibias anterior (TA) (c) and the soleus muscle (SOL) (d). The absence of the water,
Cr and Ch peaks in the marrow were expected and shows that the spatial
information is preserved. It also preserves features such as the residual
dipolar coupling of creatine in the tibialis anterior seen as a doublet, but
remains a single peak in the soleus.
Most importantly, the relayed cross peaks of
IMCL/EMCL can still be observed. Fig. 4 shows the results from EP-TOCSI
of a 42 years-old healthy volunteer
showing spectra from bone marrow (b), TA (c) and SAL (d). Here also, relayed
cross peak of IMCL/EMCL are visible demonstrating the reliability of the TOCSI
technique. Discussion:
Combining semi-LASER localization and an echo planar
readout, we have demonstrated feasibility of short
TE EP-TOCSI using the corn oil phantom and human calf muscle. Although
different versions of TOCSI have been implemented before for in-vivo brain study, this work
represents the first demonstration of a robust in vivo TOCSI for calf muscle
application. We demonstrated that TOCSI can uncover the hidden relayed cross
peaks, particularly that of the unsaturated IMCL/EMCL in calf muscle which can
play an important role in clinical application in diabetic/obese skeletal
muscle studies for better estimation of degree of unsaturation. There are still few limitations to the work
including long scan time, which will be addressed using acceleration in future
studies. Conclusion:
In this study, a new SL module for TOCSI is proposed. While
these initial results are promising, further optimization and validation with a larger pool of subjects is
needed. We expect that the new developments presented in this work will
facilitate in-vivo applications of TOCSI in clinical evaluations.Acknowledgements
This research was supported by grants from 1)
NIH/NIBIB (5R21EB020883-02) and 2) NINDS 1R21-NS090956. References
1. Mayer D, Dreher W, Leibfritz D. Fast
echo planar based correlation peak imaging: Demonstration on the rat brain in
vivo. Magn Reson Med 2000;44(1):23-28.
2. Thomas MA, Yue K, Binesh N, et al.
Localized two-dimensional shift correlated MR spectroscopy of human brain. Magn
Reson Med 2001;46(1):58-67.
3. Posse S, DeCarli C, Le Bihan D.
Three-dimensional echo-planar MR spectroscopic imaging at short echo times in
the human brain. Radiology 1994;192(3):733-738.
4. Lipnick S, Verma G, Ramadan S, et al.
Echo planar correlated spectroscopic imaging: Implementation and pilot evaluation
in human calf in vivo. Magn Reson Med 2010;64(4):947–956.
5. Nagarajan R, Carpenter CL, Lee CC, et
al. Assessment of Lipid and Metabolite Changes in Obese Calf Muscle Using
Multi-Echo Echo-planar Correlated Spectroscopic Imaging. Sci Rep.
2017;7(1):17338.
6. Wilson NE, Burns BL, Iqbal Z, Thomas MA. Correlated
spectroscopic imaging of calf muscle in three spatial dimensions using group
sparse reconstruction of undersampled single and multichannel data. Magn Reson
Med 2015;74(5):1199-1208.
7. Braunschweiler L, Ernst RR. Coherence Transfer by
Isotropic Mixing: Application to Proton Correlation Spectroscopy. J Magn Reson
1983;53(3):521–528.
8. Marjanska M, Henry PG, Ugurbil K, Gruetter R. Editing
through multiple bonds: Threonine detection. Magnetic Resonance in Medicine.
2008;59(2):245–251.
9. Marjanska M, Henry PG, Bolan PJ, et al. Uncovering hidden in vivo resonances using editing based on localized TOCSY. Magn Reson Med 2005;53(4):783-789.
10. Choi IY, Lee SP, Shen J. Selective homonuclear
Hartmann-Hahn transfer method for in vivo spectral editing in the human brain.
Magn Reson Med 2005;53(3):503–510.
11. Andronesi OC, Ramadan S, Mountford CE, Sorensen AG.
Low-power adiabatic sequences for invivo localized two-dimensional chemical
shift correlated MR spectroscopy. Magnetic Resonance in Medicine 2010;
64(6):1542–1556.
12. Andronesi OC, Gagoski BA, Adalsteinsson
E, Sorensen AG. Correlation chemical shift imaging with low-power adiabatic
pulses and constant-density spiral trajectories. NMR Biomed 2012;25(2):195–209.
13. Ugurbil K, Garwood M, Rath AR, Bendall MR. Amplitude
and Frequency/Phase-Modulated Refocusing Pulses that Induce Plane Rotations
Even in the Presence of Inhomogeneous B1 fields. Journal of Magnetic Resonance.
1988;78:472–497.
14. Levitt M, Freeman R,
Frenkiel T. Broadband heteronuclear decoupling. J Magn Reson
1982;47:328–330.
15. Ogg RJ, Kingsley PB, Taylor JS. WET, a T1- and
B1-insensitive water-suppression method for in vivo localized 1H NMR
spectroscopy. J Magn Reson B 1994;104(1):1–10.
16. Sarma MK, Huda A, Nagarajan R, et al.
Multi-dimensional MR spectroscopy: towards a better understanding of hepatic
encephalopathy. Metab Brain Dis 2011;26(3):173–184.