Rajakumar Nagarajan1,2, Maithili Gopalakrishnan2, Amir Huda3, Melissa Joines2, Nanette Debruhl2, and Michael A Thomas2
1Human Magnetic Resonance Center, Institute for Applied Life Sciences (IALS), University of Massachusetts, Amherst, MA, United States, 2Radiological Sciences, University of Califonia Los Angeles, Los Angeles, CA, United States, 3Physics, California State University, Fresno, CA, United States
Synopsis
In vivo magnetic resonance spectroscopy (MRS) of the breast can be
used to measure the level of choline-containing compounds, which is a biomarker
of malignancy. The advantage of four
dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) enables full slice coverage of the breast
facilitating recording of multi-voxel based two-dimensional (2D) MRS than the
single-voxel based localized correlated spectroscopy (L-COSY). Also in addition
to differentiate malignant from benign, EP-COSI can differentiate the healthy
fatty from glandular. Decreased ADC values derived from diffusion weighted
imaging (DWI) can be correlated with increased choline and decreased lipids
quantified by the EP-COSI technique.
Introduction
In vivo proton MRS of the breast, which
provides molecular information obtained in a noninvasive manner, has shown that
choline-containing compounds can be detected in most breast cancers 1-3,
whereas choline is generally not detectable in normal breast tissues. Single
voxel 1D MRS and a single slice-based two-dimensional
(2D) or three dimensional (3D) MRSI suffer from overlapping metabolites and also,
the MRSI scan time is long. Likewise, localized 2D correlated spectroscopy (L-COSY) 4 suffers from a voxel placement and a
long scan time. EPSI can significantly cut down the acquisition duration 5. Combining a
second spectral dimension with the EPSI sequence will increase the spatial-spectral
coverage using echo planar correlated
spectroscopic imaging (EP-COSI) which records two spectral and two spatial
dimensions 6. Diffusion weighted imaging (DWI) is a short, non-contrast MRI
sequence that has strong potential to increase specificity as an adjunct to
conventional breast MRI protocols. DWI
measures the apparent diffusion coefficient (ADC), which characterizes the
mobility of water molecules in vivo and indirectly reflects tissue cellularity,
microstructural characteristics and membrane integrity 7. Two major goals of
this work were as follows: 1) to implement and validate 4D EP-COSI in healthy fatty, glandular and breast cancer in
women, and 2) to correlate the
metabolite ratios derived from the 4D EP-COSI
data with ADC from the DWI data.Materials and Methods
The 4D EP-COSI
sequence was implemented on a Siemens 3T Tim-Trio MRI/MRS scanner (Siemens
Medical Systems, Erlangen, Germany)
as shown by Lipnick et al.6. The parameters for the EP-COSI acquisition were: TR /TE/ Average = 1500s/30ms/1, 1024 bipolar
echoes with each echo sampling 16 kx and 16 ky, FOV= 16cm. The bandwidth of
directly detected spectral dimension (F2) was 1190Hz and for the indirect
second dimension (F1), 50 increments with bandwidths of 1250Hz was
used. The individual voxel volumes in the 4D EP-COSI data were approximately 2.0ml.
Water suppressed (WS) (20 minutes) and non water suppression (NWS) (1.25 mins)
EP-COSI data were collected. 15 healthy
subjects (mean age of 45 years) and breast cancer patients (6 benign patients with
a mean age of 43 years and 5 malignant patients with a mean age of 51 years) underwent
acquisition of MRI/DWI and EP-COSI with a dedicated 4-channel phased array
breast ‘receive’ coil. For voxel placement, axial, coronal and sagittal T1- and
T2-weighted MR images were used, and the 4D EP-COSI spectra were recorded in the fatty and glandular areas
of healthy and malignant breasts. For the DWI, 2D spin-echo echo-planar imaging
(EPI) sequence (TR/TE of 3800/93ms; data matrix, 192 × 192; signal average, 3;
slice thickness, 3 mm; distance factor, 20%) in the axial plane was used.
Sensitizing diffusion gradients in three orthogonal directions with b values of
50 and 800 s/mm2 were applied. The ADC maps were created
automatically by the system from the trace-weighted images with b values of 50
and 800 s/mm2Results
The extracted
2D COSY of 52 years old healthy volunteer and various metabolites ratios of healthy glandular and fatty breast are shown in Fig.1(a-d). The extracted 2D COSY of 55 years old malignant patient and metabolites ratios of benign
and malignant patients are shown in Fig.2 (a-d). The ADC values
derived from the DWI data of healthy fatty, glandular regions (Fig.3a) and malignant, benign and healthy are shown in
Fig.3b. The
4D EP-COSI spectra recorded in breast carcinoma showed decreased peaks
representing the protons of methyl, methylene, water, methyl fat (FMETD),
methylene fat (FAT1), olefinic fat (UFD), and a peak due to the tri-methyl
protons of choline (Cho), which was not in detectable in healthy breast tissues. Discussion
Statistically significant metabolite changes (p<0.05)
were observed in the following groups: Wat/UFD, Wat/FMETD, Wat/TGFR, Wat/Fat and
Cho/Fat1 (between healthy glandular and healthy fatty). The difference in ADC
values between healthy glandular and healthy fatty and benign as well as
healthy and malignant showed statistically significant (P<0.05). In
agreement with earlier result 7, the ADC values were overlapping between malignant
and benign breast lesions. MRS changes were measurable in multiple breast
regions using the 4D EP-COSI sequence. However, the result of this pilot study
has a limitation due to the small number of malignant and benign subjects.Conclusion
An
important conclusion of this pilot study is that DWI and 4D EP-COSI data can be
acquired in the same setting and ADC values derived from DWI can be correlated
with biochemical changes. The 4D EP-COSI data enables a single slice coverage
of the breast facilitating recording of multi-voxel based 2D MRS and also able
to differentiate the healthy glandular and fatty breast. Acknowledgements
(W81XWH-10-1-0743) and (W81XWH-16-1-0524) from the Congressionally
Directed Medical Research Programs (CDMRP) Breast Cancer Research Program (BCRP).References
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