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Magnetic Resonance in Medicine 47:1059 –1064 (2002)
2D JPRESS of Human Prostates Using an Endorectal
Receiver Coil
Kenneth Yue, Alan Marumoto, Nader Binesh, and M. Albert Thomas*
A localized 2D J-resolved (JPRESS) MR spectroscopic sequence was evaluated in human prostates in vivo. Voxels of
typically 2 ml were placed in the peripheral zone of the prostate.
Eight healthy volunteers, three subjects with benign prostatic
hyperplasia, and three patients with prostatic cancer were
scanned on a 1.5T MR scanner, using a body coil for RF transmission and a pelvic phased-array coil combined with a disposable endorectal coil for signal reception. The total acquisition
time for a 2D JPRESS spectrum was approximately 17 min. A
major advantage of the endorectal 2D JPRESS was the ability to
resolve the peaks of choline-containing compounds and those
of spermine unequivocally. Spectral results clearly showed the
biochemical changes in cancer and benign compared to
healthy prostates, in conformity with ex vivo biochemical findings. The preliminary results suggest that the endorectal 2D
JPRESS could be successfully implemented for the diagnostic
examination of human prostates. Magn Reson Med 47:
1059 –1064, 2002. © 2002 Wiley-Liss, Inc.
Key words: 2D JPRESS; prostate; spermine; endorectal coil
The prostate is one of the most diseased human organs in
men beyond the age of 60 (1). The current diagnostic
routine usually begins with a digital rectal examination
and is often followed by a prostate-specific antigen (PSA)
blood test. Unfortunately, these tests suffer from the lack of
specificity for differentiating prostate cancers (PCa) from
benign conditions such as benign prostatic hyperplasia
(BPH) or prostatitis. Furthermore, these tests are not particularly sensitive and PCa may only become evident
when malignant cells have metastasized beyond the capsular region of the prostate (1,2). More sensitive and specific tests such as ultrasound-guided biopsy are available
but are considerably more invasive and costly (2).
A decade ago, Thomas et al. (3) used an endorectal coil
for both excitation and reception to record proton (1H) MR
spectra in healthy human volunteers and PCa patients.
Water-suppressed 1H MR spectra were recorded using a
binomial (1331, 2662) spin-echo sequence for a combined
water suppression and signal excitation (3). Moreover, the
earlier work of Schnall et al. (4) and the subsequent work
of others have revolutionized prostate MR imaging and
spectroscopy (MRI/MRS) by using an expandable endorectal receiver coil, which can be combined with an external
Department of Radiological Sciences, School of Medicine, University of California, Los Angeles, California.
Grant sponsor: Cancer Research Fund; Grant number: Interagency agreement 97-12013 (University of California, Contract 98-00924V) with the Department of Health Services, Cancer Research Program.
Presented at both the 8th ISMRM Meeting, Denver, 2000, and the 86th RSNA
Meeting, Chicago, 2000.
*Correspondence to: M. Albert Thomas, Ph.D., Radiological Sciences, UCLA
School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095-1721.
E-mail: [email protected]
Received 6 June 2001; revised 6 February 2002; accepted 7 February 2002.
DOI 10.1002/mrm.10160
Published online in Wiley InterScience (www.interscience.wiley.com).
© 2002 Wiley-Liss, Inc.
pelvic phased-array (PPA) coil, providing MRI coverage of
the prostate and the pelvis (4 –11). These methodologies
are now routinely used at many institutions.
MR spectroscopic data can be threshold-adjusted and
overlaid on MR images. Scheidler et al. (8) attempted to
assess the efficacy of the combined MRI and 3D 1H MR
spectroscopic imaging (MRSI) in detection and localization of PCa. Using the (choline⫹creatine)/citrate ratio,
Kurhanewicz et al. (9,10) assessed whether MRSI in combination with MRI could improve PCa localization in postprostate biopsy cases. Parivar et al. (11) applied prostate
MRI/MRSI for follow-up of PCa in patients who underwent cryosurgery.
The polyamines putrescine, spermidine, and spermine
are polycationic amines that are present in most living
organisms and may be important physiological markers
(12–16). Previous in vivo 1H MR prostate spectra were
one-dimensional and could not resolve these polyamines
due to the overlapping resonance of these metabolites at
1.5T. In particular, the overlaps of creatine, polyamines,
and choline-containing compounds severely limited an
unambiguous differentiation of polyamines from trimethyl
amines, namely, the choline residues.
The purpose of our study is to investigate whether 2D
JPRESS (17–19) can be applied to the human prostate in
vivo using an endorectal probe. Furthermore, we attempt
to demonstrate that 2D MRS can resolve the peaks due to
choline-containing compounds (Cho), citrate (Cit), creatine (Cr), and polyamines such as spermine (Spm) for the
detection of the underlying metabolic changes in PCa and
in BPH vs. healthy prostates.
MATERIALS AND METHODS
Subject Selection
A group of eight healthy volunteers, three BPH subjects,
and three PCa patients were recruited. For the patient
group, the MRS studies were done after fine-needle biopsy.
All aspects of the study were explained to the subjects
prior to the commencement of the study and informed
consent was obtained in keeping with the institutional
review board (IRB) guidelines.
Data Acquisition
A localized 2D JPRESS sequence was implemented on a
1.5T Signa Horizon MRI/MRS scanner (GE Medical Systems, Waukesha, WI) with a gradient strength of 2.2 G/cm
and a rise time of 248 ␮s for spectroscopy. Single voxel 3D
localization was achieved by the 2D analog of PRESS sequence, consisting of three slice-selective RF pulses (90°,
180°, 180°), optimized using the Shinnar-Le Roux (SLR)
algorithm. Water suppression was achieved by a CHESS
sequence prior to voxel localization and 1024 t2 complex
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Yue et al.
FIG. 1. a: 2D JPRESS spectrum of a composite prostate phantom containing 25 mM citrate, 10 mM spermine, 5 mM creatine, and 2 mM
free choline at pH ⫽ 7.2 (27 ml, TR ⫽ 2 sec, TE ⫽ 30 ms). b: Simulated 2D JPRESS spectrum of citrate using J ⫽ 15.6 Hz and ␦ ⫽ 9.6 Hz
at 1.5T (TR ⫽ 2 s, TE ⫽ 30 ms, 256 F1 points, and 4096 F2 points). [Color figure can be viewed in the online issue, which is available at
www.interscience.wiley.com.]
points were acquired for each FID. The additional J-resolved spectral dimension was obtained by inserting two
symmetric t1 increments of 5 ms each—first between the
two refocusing 180° RF pulses and, second, immediately
before the acquisition filter. Two-step phase cycling
schemes were used on all three pulses, resulting in a total
of eight cycling steps in conjunction with signal averaging.
Further details of the 2D JPRESS sequence can be found
elsewhere (17–19).
For the phantom study, a head coil (GE Medical Systems, Milwaukee, WI) was used for both RF transmission
and reception and the total acquisition time was 34 min
(TR ⫽ 2 sec, TE ⫽ 30 ms, 64 t1 points, and 16 NEX). For the
in vivo studies, the RF pulses were transmitted through a
body coil and the signal was received by an endorectal
surface coil configured with a PPA coil (MEDRAD, Pittsburgh, PA). The placement of the endorectal probe was
done by an experienced radiologist (AM). The bulb was
inflated with 90 –120 c.c. of air so that the plane of the
surface coil, indicated by a marker along the handle, was
in the closest proximity to the prostate tissue. MR spectroscopic voxel was prescribed on an axial fast spin-echo MRI
optimized for prostate tissue contrast: 4-mm slice, TR ⫽
2.5 sec, TE ⫽ 84 ms, FOV ⫽ 14-24 cm, acquisition matrix
256 ⫻ 192, and 4 NEX, resulting in an acquisition time of
4 min. The spectroscopic acquisition time per voxel location was 11–17 min (TR ⫽ 2 sec, TE ⫽ 30 ms, 40 – 64 t1
points, and 8 NEX). Combined with an approximately
7-min voxel prescription, shimming, and prescan optimization, the total measurement time was within 30 min for
one spectroscopic location and less than an hour for two
locations. When the full width at half maximum (FWHM)
of water peak was greater than 10 Hz, the voxel shimming
procedure was repeated. Typically, a 7-Hz FWHM of unsuppressed water signal was observed prior to 2D JPRESS
acquisition.
Data Processing
The 2D MRS raw files were transferred to an SGI O2
workstation (Silicon Graphics, Sunnyvale, CA) for offline
data processing using Felix98 (Molecular Simulations, San
Diego, CA). The raw matrix was apodized with phaseshifted sinebell squared functions along t1 and t2 and
zero-filled to 128 ⫻ 2048 prior to Fast Fourier Transformation. All 2D spectra were presented as contour plots and
the 2D spectral matrices were not skewed by 45° about J ⫽
0 Hz (18,20). Hence, the 2D J-resolved peaks due to weakly
coupled protons were expected to be aligned on straight
lines 45° with respect to the F2 axis and more complex
patterns were expected for strongly coupled spin systems (20).
RESULTS
Figure 1a shows a 2D JPRESS spectrum of a composite
prostate phantom containing free Cho, Cit, Cr, and Spm at
pH ⫽ 7.2. A 27-ml voxel was localized. Shown in Fig. 1b
is a simulated hard pulse version of 2D JPRESS (90°, 180°,
180°) spectrum of Cit using the GAMMA simulation li-
2D JPRESS of Prostate Using Endorectal Coil
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FIG. 2. 2D JPRESS spectrum (a) of a 28-year-old healthy subject and (b) its corresponding 2 ml voxel placement. [Color figure can be
viewed in the online issue, which is available at www.interscience.wiley.com.]
brary (21). Cit has two equivalent methylene groups. Each
proton pair forms a strongly J-coupled AB spin system
(20,22), resulting in eight J-resolved 2D peaks antisymmetric about F2 ⫽ 2.65 ppm, as evident in the experimental
and simulated 2D spectra. The 2D peaks located along
F1 ⫽ ⫾1.6 Hz, ⫾7.8 Hz, and ⫾16.4 Hz were in agreement
with a previous report (20). In addition, the projected 1D
spectra onto F1 and F2 axes are also shown in Fig. 1b.
Regarding other metabolites, the region between 3–
4 ppm had several overlapping peaks along F1 ⫽ 0 Hz: Cr
(3.0, 3.9 ppm), Cho tri-methyl singlet (3.2 ppm), Cho methylene multiplets (3.5, 4.0 ppm), and polyamines such as
Spm (multiplets at 2.1 and 3.1 ppm). The J-resolved peaks
of Cho at F2 ⫽ 3.5 ppm and 4.0 ppm were not readily
observable here at 2 mM, although their presence has been
confirmed at a higher concentration of 10 mM (18). On the
other hand, the J-resolved peaks of Spm methylene protons were well isolated, as shown around the regions of
F2 ⫽ 2.1 ppm and 3.1 ppm. Since the methylene protons of
Spm follow weak J-coupling (Chemical shift difference Ⰷ
J), the triplet centered at F2 ⫽ 3.1 ppm (F1 ⫽ 0 Hz and ⫾7.3
Hz) was clearly visible. 2D J-resolved peaks due to Cr were
not resolvable in Fig. 1a due to a limited spectral dispersion along F1.
Figure 2 shows a 2D JPRESS spectrum of a 28-year-old
healthy prostate using a 2-ml voxel. The presence of strong
Cit peaks was consistent with the well-known fact of its
high abundance in healthy prostate (3,10). Averaged over
the eight healthy controls, the 2D peaks due to Cit were
located along F1 ⫽ ⫾1.6 Hz, ⫾7.9 Hz, and ⫾17.5 Hz. In
addition, the triplet nicely resolved about F2 ⫽ 3.1 ppm
along F1 ⫽ 0 Hz and ⫾7.8 Hz was identified as Spm. Also,
there were 2D peaks along F1 ⫽ 0 Hz due to Cr and Cho at
F2 ⫽ 3.0 ppm and 3.2 ppm, respectively. Moreover, the
J-resolved peaks due to Cho methylene protons were unobservable due to the small voxel size and reduced number of averages.
Figure 3 shows a 2D JPRESS spectrum from a 2.25-ml
voxel of a 60-year-old subject with BPH. More intense 2D
cross peaks were indicative of an increase of Cit in BPH, as
confirmed by previous 1D MRS reports (10). The locations
of Cit peaks were comparable to that of healthy prostate.
Although no considerable change of Cho was observed, a
slight elevation of Spm was indicated.
Figure 4 shows a 2D JPRESS spectrum from a 2-ml voxel
of a 79-year-old patient with PCa. The three 2D peaks due
to the methylene protons of Spm centered at F2 ⫽ 3.1 ppm
were reduced remarkably in the two patients, along with a
moderate increase of Cho. The 2D peak changes of Spm
were minimal in the third PCa patient with a decrease of
Cho. Compared to the spectra of healthy controls and BPH,
a strong depletion of Cit was also evident in the entire
group of PCa patients.
Selected 2D peaks were quantified in the following regions (F1, F2): Cit (⫾7.9 Hz, 2.62–2.68 ppm), Spm (7.8 Hz,
3.05 ppm), and Cho⫹Spm⫹Cr (0 Hz, 3.0 –3.2 ppm). Their
ratios (mean ⫾ SD) in healthy controls, BPH, and PCa
were: 1) Cit/Cho⫹Spm⫹Cr ⫽ 0.71 ⫾ 0.20 (n ⫽ 8), 0.65 ⫾
0.68 (n ⫽ 3), and 0.18 ⫾ 0.06 (n ⫽ 3); 2) Spm/
Cho⫹Spm⫹Cr ⫽ 0.42 ⫾ 0.16 (n ⫽ 8), 0.54 ⫾ 0.49 (n ⫽ 3),
and 0.21 ⫾ 0.24 (n ⫽ 3), respectively.
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Yue et al.
FIG. 3. 2D JPRESS spectrum (a) of a 60-year-old subject with BPH and (b) its corresponding 2.25 ml voxel placement. [Color figure can
be viewed in the online issue, which is available at www.interscience.wiley.com.]
FIG. 4. 2D JPRESS spectrum (a) of a 79-year-old patient with PCa and (b) its corresponding 2 ml voxel placement. [Color figure can be
viewed in the online issue, which is available at www.interscience.wiley.com.]
2D JPRESS of Prostate Using Endorectal Coil
DISCUSSION
A major problem with the 1D MRS or MRSI prostate data
is the significant overlap of Cr, Spm, and Cho in the spectral range of 3.0 –3.2 ppm. 2D JPRESS clearly resolved the
cross peaks due to Spm, separated by ⬃8 Hz about F1 ⫽
0 ppm. Strong coupling effects in the 2D JPRESS spectra of
human brain were reported earlier (18). The endorectal 2D
JPRESS spectra of prostate showed similar effects for Cit
and Cho.
The T2 value of Cho is 227 ⫾ 61 ms (6), while that of
polyamines is still unknown. Therefore, a short TE of
30 ms was chosen to optimize the initial signals from every
metabolite, including the signals from the short T2 metabolites.
There is a definite need to quantify polyamines in vivo,
since it has been reported that high concentration of Spm
(10 –20 mM) may be responsible for the slow growth of
cancer cells in prostatic tissue. However, previous biochemical analyses of polyamines in PCa resulted in conflicting findings (12–15). Urinary excretion of spermidine
was significantly elevated in prostatic carcinoma as compared to a control group of patients (13). Although there
was no difference between the Spm levels of BPH and
controls, Spm of PCa was elevated in expressed prostatic
secretion (14). Plasma Spm levels were only occasionally
elevated in PCa compared to normal prostate (15).
In this study, the 2D cross peaks due to the methylene
protons of Spm centered at F2 ⫽ 3.1 ppm were reduced
remarkably in PCa patients (Fig. 4a), but slightly elevated
in BPH patients (Fig. 3a). Our results were in good agreement with a recent ex vivo MRS and high performance
liquid chromatography (HPLC) analysis of prostatic tissue (12).
Although the polyamines include putrescine, spermine,
and spermidine, the 2D JPRESS cross peaks of these different polyamines were not resolved. However, the MRS
peaks due to different polyamines could be detected unequivocally using heteronuclear single quantum coherence spectroscopy (16).
The 2D contour plots used in this study may not permit
accurate measurements of peak positions and multiplet
separations. Depending on the postprocessing parameters,
the centroid of a 2D peak can easily shift along the F1 axis.
In strongly coupled spin systems (20), this dependency
becomes even more pronounced, which accounts for the
discrepancies between the in vitro and the in vivo F1
results of Cit and Spm, as shown above.
As an alternative, 2D cross sectional slices were used in
the oversampled 2D J-resolved spectra of human prostate
without presaturation of water (23). A drawback is that the
sensitivity of 2D cross-sections is often affected by t1-noise
or ridge (24). This causes noise bands at the 2D peak
locations running parallel to the F1 axis. The t1-noise results from either random fluctuation of the scanner or due
to subject’s motion. In our study, the strong t1-ridges recorded in two healthy controls were possibly due to the
subject’s movement.
The single-voxel 2D JPRESS suffers from some drawbacks. The voxel size and its location must be selected at
the time of acquisition and the time constraints limit the
number of voxels to one or two per session. In this study,
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we selected one single voxel located predominantly in the
peripheral zone of the prostate, where cancer lesions are
commonly found. Another major drawback of a singlevoxel-based technique is that one may even miss the
target lesion in PCa. Partial volume effect will be more
severe while the voxel size is large (⬎1 ml). Hence, it is
worthwhile to investigate a 2D JPRESS analog of MRSI
while keeping a reasonable acquisition time in prostate
studies (25).
In comparison with the recently proposed 2D L-COSY
(26), 2D JPRESS has a narrower spectral window along F1.
Hence, the number of t1 increments (⌬t1) can be reduced in
2D JPRESS, resulting in a shorter total acquisition time. In
addition, 2D JPRESS has superior sensitivity compared to
2D L-COSY, allowing a voxel size of as small as 1–2 ml.
However, the strong coupling effect leads to more complex
2D J-resolved peaks at 1.5T than the weakly coupled protons, resulting in a difficult task of quantitation. In 2D
L-COSY, there are no additional cross peaks due to the
strong coupling; however, the cross peak intensities are
weighted accordingly (20,24). Our concurrent effort focuses on the evaluation of endorectal 2D L-COSY in human prostates, where an improved spectral dispersion is
expected to improve the quantitation of prostate metabolites.
In conclusion, our observations suggest that spatially
localized endorectal 2D JPRESS spectra can be successfully recorded using a clinical 1.5T MR scanner. The pilot
results show that 2D JPRESS peaks due to Cit and Spm can
be resolved and the changes in these metabolite levels can
be successfully quantified in BPH and PCa patients compared to healthy controls. The results are consistent with
the previous 1D MRS and biochemical findings. In particular, our results with a limited number of patients demonstrate that the Spm peaks are reduced in PCa and
slightly increased in BPH, in agreement with a recent
study using prostatic tissue (12).
ACKNOWLEDGMENTS
The authors thank Dr. Zoran Barbaric and Dr. Shantanu
Sinha for scientific assistance and Dr. Dirk Mayer and Dr.
Wolfgang Dreher for sample GAMMA programs. The authors also thank Mrs. and Mr. Raman for assistance in
recording the earlier 2D JPRESS spectra.
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