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MRSI IN THE MANAGEMENT OF PROSTATE CANCER
NAYYAR
et al.
BJUI
Magnetic resonance spectroscopic imaging:
current status in the management of
prostate cancer
BJU INTERNATIONAL
Rishi Nayyar, Rajeev Kumar, Virendra Kumar*,
Naranamangalam R. Jagannathan*, Narmada P. Gupta and Ashok K. Hemal
Departments of Urology and *NMR, All India Institute of Medical Sciences, New Delhi, India
Accepted for publication 17 December 2008
In the past decade several advances have
been made in the field of nuclear magnetic
resonance (NMR) imaging. MR spectroscopic
imaging (MRSI) is one such advance which
holds promise for detecting biochemical
change on imaging of the prostate, and that
INTRODUCTION
Prostate cancer is common and remains the
second leading cause of cancer death among
elderly men. Current methods for its
detection, i.e. a DRE, TRUS, PSA assay and
even sextant biopsy have limited accuracy for
most early prostate cancers. This challenge
in diagnosis, localization and staging of
potentially curable early disease has
prompted further research into radiological
imaging which could be more specific and
sensitive, and that provides good positive/
negative predictive value (PPV/NPV).
MRI is well known for its diagnostic potential,
primarily due to its capability to noninvasively
generate high-resolution anatomical
images based on various inherent tissue
characteristics. With ongoing research on
ways of data acquisition during MRI and their
analysis, newer sequences and strategies have
been developed that provide more specific
information (diffusion imaging, functional
imaging, metabolic imaging, etc.), faster
image generation and higher resolution. With
these newer technologies, the diagnostic
potential of MR techniques is improving
further, and its indications are also
developing. MR spectroscopic imaging (MRSI)
is one of these new promising techniques, and
uses the regular MRI machine, requiring only
software upgrades as an additional cost
factor.
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can be used in several ways for improving
the management of patients with prostate
cancer. We review the literature, technique
and basics of MRSI, with its current status
in various situations as applied to the
management of prostate cancer.
KEYWORDS
MRSI: PRINCIPLES, DATA ACQUISITION
AND BASIS FOR DIAGNOSIS OF
PROSTATE CANCER
metabolites or biochemical species that are
at low concentration.
The detailed description of MRI/MRSI is
outside the purview of this clinical article
and interested readers are referred to
radiological textbooks and other review
articles [1]. Only the salient features are
highlighted here. All MR techniques are
based on the phenomenon of nuclear
magnetic resonance (NMR). In vivo MRS of
organs and tissues is an extension of highresolution NMR spectroscopy and is based on
the resonance of protons in the nuclei of
different chemical constituents of the tissue.
When placed in a homogenous magnetic
field, the different protons present in a
molecule do not experience the same
magnetic field depending upon the amount
of shielding of the nucleus inherent in the
molecular structure, and therefore resonate
differently. The main difference between MRI
and MRS is that in MRI the signal is acquired
in the presence of magnetic-field gradients,
while for MRS it is necessary to have a
homogenous magnetic field to observe the
chemical shift differences of metabolites and
therefore, no magnetic field gradient is
applied during signal acquisition. In MRI,
signals originating from protons (1H) present
in water and fat are recorded to generate
images, while the purpose of MRS is to
detect signals from 1H present in other
BIOCHEMICAL BASIS FOR DIAGNOSIS OF
PROSTATE CANCER ON MRSI
magnetic resonance spectroscopy, prostate
cancer imaging, prostate cancer
The prostate gland has the unique feature
of producing extraordinarily high levels
of citrate from the epithelial cells of
peripheral zone (PZ) [2]. This occurs due to
a limiting activity of the enzyme ‘aconitase’
which converts citrate to isocitrate, in the
first step of the Krebs cycle. This enzyme is
inhibited by the presence of high levels of
mitochondrial zinc, which is another unique
feature of the prostate (Fig. 1). Normal
prostate and BPH tissue contain citrate
levels of 8000–15 000 nmol/g while all
other tissues contain 150–450 nmol/g.
However, in prostate cancer the levels of
zinc are low and the tissue citrate levels
are decreased to 1000–2000 nmol/g. In
contrast to citrate, choline levels increase
in prostate cancer due to changes in cell
membrane synthesis and degradation that
occurs with the development of human
cancers [3]. These metabolic changes in
prostate tissue might occur before
morphological changes in tissues [4] and
theoretically might be of value in detecting
latent, unsuspected prostate cancer where
routine histological sections have failed to
detect malignancy.
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MRSI IN THE MANAGEMENT OF PROSTATE CANCER
FIG. 1. The citrate synthesis pathway in normal prostate epithelial cells. High levels of intramitochondrial zinc
inhibit aconitase activity, which limits the conversion of citrate to isocitrate. This results into net citrate
production by the prostate.
FIG. 2. (A) A spectrum from one voxel; (B) a spectral
map; and (C) a metabolite-ratio map of the prostate
in a patient with a PSA level of 8.9 ng/mL.
a
Glucose
Basilar surface
Cit
Cell membrane
Pyruvate
0.2
Acetyl CoA
0.1
Mitochondria
Cr
Citrate
Oxaloacetate
Aconitase
TCA
Cycle
Malate
Cho
Zn++
0.0
4
3
2
ppm
1
Isocitrate
b
Succinate
α-Ketoglutarate
Cytoplasm
Acinar lumen
Citrate
c
MRSI DATA ACQUISITION AND CRITERIA TO
DIAGNOSE PROSTATE CANCER
MRS is based on the detection of different
metabolites that have characteristic
resonant frequency (primarily determined by
the chemical structure). In vitro MRS refers
to MRS of extracts of tissues, while in vivo
MRS refers to obtaining a spectrum from an
anatomically defined region noninvasively.
Some widely used localization schemes [1]
used for in vivo MRS are: (i) Surface-coil
localization; (ii) depth-resolved surface-coil
spectroscopy; (iii) single-voxel spectroscopy;
and (iv) spectroscopic imaging. MRSI (also
called multivoxel spectroscopy or chemical
shift imaging) is a method for collecting
spectroscopic data from multiple voxels
covering a large volume of interest in
a single measurement. It allows the
acquisition of spectra from smaller voxels
than single-voxel techniques. After
acquisition of data, it can be examined as
single spectra, a spectral map or metabolite
images (Fig. 2). Both spectral maps and
metabolite images can be overlaid on the
MR image.
©
The MRSI data can be obtained within the
same examination as the endorectal MRI. All
data are acquired using a scanner system
which consists of a solenoid, superconducting
magnet that produces a strong and highly
homogeneous magnetic field (B0) across the
imaging volume (Fig. 3a). Gradient coils, shim
coils and radiofrequency (RF) coils are also
placed inside the magnet. Gradient coils
produce additional linear electromagnetic
fields to systematically vary B0 in any
direction. Shim coils are used to compensate
for B0 inhomogeneities. RF coils generate a B1
field used to excite the spins, and to detect the
signals originating from the sample. The RF
coil permanently installed in the MR system is
the body coil. RF coils are relatively simple
circuits and can be changed in design
depending on the application. Dedicated
surface coils, with geometry optimized for
specific body parts, can be used to receive the
RF signal with greater sensitivity. The use of
the endorectal surface coil has made possible
three-dimensional (3D) MRSI of prostate with
better sensitivity (Fig. 3b). MRI with a body
coil (Fig. 3c) lacks sufficient resolution to
show fine anatomical details of the prostate
and periprostatic tissues [5]. Currently, the
resolution of MRSI with machines of 1.5 T is
a voxel size of ≈0.3 cm3. However, better
resolution is possible with 3 T, and is <0.2 cm3.
An endorectal coil is inserted using lignocaine
jelly. The total 3D MRSI examination time,
including patient positioning, coil placement,
imaging and spectroscopy, is ≈1 h. Then
localizer images are acquired on a ‘True
fast imaging with steady state precession’
sequence and the correct position of the
endorectal coil is checked. These sagittal
images are used to plan T2-weighted sagittal
images, which in turn are used to plan T2weighted coronal images. Finally, T2-weighted
transverse images are planned on coronal and
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FIG. 3. (a) 1.5 T whole-body MR scanner, showing the
position of the patient in the scanner and the
direction of magnetic field; (b) an endorectal coil;
and (c) a body-flex array coil.
TABLE 1 Metabolite ratio from various MRS studies to differentiate between benign and malignant
prostate tissue
Reference
[7]
[8]
[9]
[10]
[11]
[12]
Method
SVS
MRSI
MRSI
MRSI
SVS
MRSI
Metabolite ratio
citrate/choline + creatinine
choline + creatinine/citrate
choline + creatinine/citrate
choline + creatinine/citrate
citrate/choline + creatinine
choline + creatinine/citrate
Mean (SD) metabolite ratio for PZ
Normal
Cancer
1.28 (0.14)
0.67 (0.17)
0.54 (0.11)
2.1 (1.3) (>0.86)
–
2.1 (1.3)
0.22 (0.13)
1.62 (2.08)
2.16 (0.56)
0.31 (0.25)
–
>0.68
BPH
1.21 (0.29)
–
–
–
1.43 (0.58)
–
SVS, single-voxel spectroscopy.
MRSI at our centre are: TR 1300 or 650 ms, TE
120 ms, voxel size 5 × 5 × 5 mm3, average 3,
with a total acquisition time of 17 min. All
spectroscopic data processing is then carried
out using pre-loaded software. The spectrum
from individual voxels is Fourier-transformed,
frequency aligned, phased, and if needed,
baseline corrected [6].
sagittal images, keeping transverse images
perpendicular to the craniocaudal axis of the
prostate. Images are then acquired covering
the entire prostate using a turbo spin echo
sequence, with a repetition time (TR) of
2200–5000 ms, an echo time (TE) of 98 ms,
field of view of 280, a matrix size 256 × 256
and a slice thickness of 5 mm, with no
interslice gap. For MRSI, a point-resolved
spectroscopy localized 3D-MRSI sequence is
used. A ‘MEGA’ pulse is used for simultaneous
suppression of lipid and water. The
suppression of signals from peri-prostatic
fatty tissue is similarly essential, as it can
produce false-positive results. Six to eight
outer-volume saturation bands are used
to suppress the signal originating from
periprostatic fatty tissue. Manual shimming
can be used to achieve a line width of <24 Hz
(full width at half maximum). An MRSI matrix
with scan resolution of 16 × 16 × 8
(interpolated to 16 × 16 × 16) is used in the
weighted acquisition mode, optimizing the
signal-to-noise ratio (SNR) obtained per unit
measurement time. The parameters used for
1616
To calculate the metabolite ratio [citrate/
(choline + creatinine)], the area under each
peak of the spectrum is determined on the
basis of resonance position and peak widths.
On MRSI, choline, creatine and citrate have
distinctive peaks resonating at 3.2, 3.0 and
2.6 ppm, respectively (Fig. 2a). The metabolite
ratio is calculated from peak integral values
determined for each peak. Creatinine is added
to choline because the spectrum of creatinine
lies very close to choline and clinically
sometimes it might not be possible to
differentiate between the spectra. The values
of the metabolite ratio in normal PZ, cancer
and BPH tissue, as given in a few reports, are
shown in Table 1 [7–12]. Polyamine is another
new metabolite whose peak can now be
resolved at 3.1 ppm with the newer
spectroscopic sequences and MRI machines
of higher magnetic field strength [13]. Unlike
choline, this polyamine peak decreases in the
presence of prostate cancer. Shukla-Dave
et al. [14] recently reported a statistically
based classification rule for identifying voxels
containing cancer based on both the
(choline + creatine)/citrate ratio and the
polyamine peak.
FACTORS INFLUENCING THE RESULT
OF MRSI
Standardization of the technique of data
acquisition and interpretation is mandatory
for MRSI, as it is not widely practised. The size
and shape of the endorectal/surface coils, the
alignment of the coil with respect to the
prostate, distance of the voxel from the
receptor coils, the size of the voxels, volumeaveraging effect, SNR, mixing of signals from
the nearby tissues like seminal vesicles (that
have high choline levels), lipid contamination,
the definition of a threshold ratio for
malignancy, movement of the patient during
data acquisition, etc., are some factors that
might directly influence the outcome of MRSI
in any patient. MRSI should therefore be
interpreted considering all the possible
misleading factors.
STATUS OF MRI/MRSI FOR THE CLINICAL
DIAGNOSIS OF PROSTATE CANCER
On MRI, prostate cancer is usually seen as a
low signal-intensity lesion in a hyperintense
PZ on a T2-weighted image. This is due to
increased cell density and a loss of the
prostatic ducts compared to the healthy
tissue. MRI alone has relatively poor
specificity, with false-positives resulting from
other conditions like biopsy artefacts, fibrosis,
prostatitis, hyperplastic nodules and posttreatment changes which also appear
hypointense. The combined use of endorectal
and phased-array coils allows improved
accuracy of MRI up to 75–90% [15], and a
sensitivity and specificity of 61–77% and
46–81%, respectively [16].
MRSI differentiates between benign and
malignant tissue based on metabolic changes
(Fig. 4). A (choline + creatinine)/citrate ratio of
>0.86 or citrate/(choline + creatinine) of <1.4
was found to be a very specific marker for
prostate cancer, with 98% of the cancer ratios
falling above three SDs of the mean healthy
PZ value [8]. However, despite the initial
enthusiasm it has not been able to replace the
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FIG. 4. Representative 3D MRSI spectra obtained from the PZ of the prostate from (a), a normal volunteer
(aged 28 years), (b) a patient with BPH, and (c) a patient with malignancy in the PZ.
a
b
Cit
Cit
was high and approaching 100%. Even on
following the patients for >2 years the high
NPV of MRSI was maintained [22]. This fact
might help in selecting cases where TRUSguided biopsy might not be required even in
presence of a raised PSA level.
0.3
STATUS FOR LOCATING PROSTATE CANCER
AND IMPROVING CANCER DETECTION
RATES ON BIOPSY
0.2
0.2
0.0
4
Cr
Cho
Cr
0.1
Cho
0.1
3
2
ppm
1
0.0
4
3
2
ppm
1
Cho
c
0.08
0.06
0.04
Cit
Cr
0.02
0.00
4
3
2
ppm
1
biopsy as a clinical means to diagnose prostate
cancer. False-positive results could arise from
signal contamination from the seminal
vesicles, assigning a noise level to
undetectable peaks to calculate a metabolite
ratio, chronic prostatitis, high-grade prostatic
intraepithelial neoplasia, previous biopsy,
small gland, etc. False-negative results could
arise from the volume-averaging effect (signal
from a small malignant focus being averaged
out with the signals from the surrounding
benign tissue), failure to take a biopsy exactly
from the malignant voxel on MRSI, tumour in
the transition zone (TZ), etc. Moreover, the
differentiation of benign vs malignant tissue is
presently limited to the PZ only. Even though
metabolites can be evaluated throughout the
gland [17,18], there are no established criteria
for identifying ‘cancerous’ voxels on MRSI in
the TZ. Due to stromal BPH, glandular BPH and
chronic prostatitis, the choline- and citratebased ratios overlap considerably between the
benign and malignant groups in the central/
©
TZ. Further, there are variations in metabolite
levels near the ejaculatory duct.
Considered alone, 3D MRSI has higher
specificity for identifying cancer than MRI.
However, they can be combined to improve
the ability to identify cancer within the
prostate. Scheidler et al. [16] showed that
high specificity (91%) was obtained when
combined MRI/3D MRSI indicated cancer,
whereas a high sensitivity (95%) was obtained
when either test provided a positive result.
Comparison of MRI/3D MRSI data with stepsection histology of the prostate has shown a
higher sensitivity, specificity and PPV than
standard sextant biopsy of the prostate
[19,20].
Our studies on this subject have shown the
sensitivity, specificity, positive and NPV to be
98%, 40%, 43% and 97%, respectively, for
MRSI in the diagnosis of prostate cancer [21].
Even though the PPV remains poor, the NPV
TRUS biopsies are limited by a low sensitivity
of 60%, a PPV of only 25% and false-negative
rate estimated to be as high as 15–34%
[23,24]. Combining MRSI with TRUS-guided
biopsy could help in (i) directing biopsy to the
suspicious area and therefore improve its
detection rate, and (ii) avoiding the biopsy in
those who have no suspicious lesions and
therefore avoiding all risks associated with an
invasive biopsy.
3D MRSI data can be overlaid on
corresponding T2-weighted MRI images to
identify the anatomical and pathological
location of spectroscopic voxels. Tri-planar
coordinates of the suspicious area can thus be
obtained and used to take a biopsy from the
suspicious area under TRUS guidance [25]. The
addition of MRSI to MRI has been shown to
improve the localization of cancer to a sextant
of the prostate, with a sensitivity of up to
95% and a specificity of 91% when compared
with MRI alone (P < 0.05) [16,26]. We
prospectively evaluated the role of MRI/MRSI
in men with a PSA level of <10 ng/mL, who
have poorest cancer detection rate and the
highest false-negative rate on TRUS biopsy,
and found a cancer detection rate about three
times better, and a NPV approaching 100%
[21,25].
The TRUS biopsy probe is obliquely directed on
to the prostate while the voxels on MRI/MRSI
are in the vertical or horizontal planes. This
might make it difficult to exactly overlay the
coordinates obtained from the MRI on to
the image during TRUS. Therefore MRIcompatible biopsy systems have been
developed that can help to guide the biopsy,
thereby totally avoiding TRUS [27].
STATUS FOR FOLLOW-UP OF PATIENTS
WITH RAISED PSA LEVELS AND SELECTION
FOR REPEAT BIOPSY
Besides biochemical imaging with a high
NPV, 3D MRSI also makes the analysis of the
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entire prostate gland in vivo possible. This
is unlike the needle-core biopsy, which
analyses only a small fraction of prostatic
tissue. Thus, MRSI can be used as an
additional measure to exclude carcinoma in
a patient who has a raised PSA level but a
benign biopsy report. This might help in
selecting cases for a repeat biopsy, thereby
avoiding risks of repeated saturation core
biopsies in those with no suspicious voxels,
and improving the detection rate of those
who undergo repeat biopsy by directing
biopsies to suspicious areas [28,29]. We have
shown that MRSI-negative cases with a PSA
level of <10 ng/mL and one negative biopsy
report can be safely followed with PSA levels
alone [22].
STATUS FOR TUMOUR GRADING AND
TUMOUR VOLUME MEASUREMENT FOR
DIFFERENTIATING BETWEEN CLINICALLY
SIGNIFICANT AND INSIGNIFICANT
CANCERS
Choline increases and citrate reduction
have been reported to be related to the
aggressiveness of prostate cancer and
Gleason grade. The choline concentration was
the most significant predictor of Gleason
score, being significantly (P < 0.001) higher
in high-grade (Gleason >7) than moderate
grade (Gleason <7) cancers [30,31]. Due to
considerable heterogeneity of prostate
cancers and biopsy sampling errors, cancers
are often not detected or inaccurately graded
on biopsy. In these cases 3D MRSI might help
in correct grading by analysing the entire
gland noninvasively, and thus providing a
better preoperative prediction of Gleason
grade. This information can be important in
cases where the choice of treatment is
critically dependent on Gleason grade. In
these cases, further confirmation of the
highest grade of the tumour might be
obtained by directing the biopsy to the area
suspected of harbouring the highest grade of
cancer on MRSI.
Although adding 3D MRSI to MRI has been
shown to increase the overall accuracy of
measuring the prostate tumour volume,
the variability in measurement limits the
consistent quantitative tumour volume
estimation, particularly for small tumours
[26]. Therefore, the role of MRSI/MRI in
differentiating significant and insignificant
tumours based on tumour volume remains
uncertain.
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STATUS FOR STAGING OF PROSTATE
CANCER: CAPSULAR, SEMINAL VESICLE
AND LYMPH NODE INVOLVEMENT
Knowledge of the spread of cancer beyond
the prostate capsule is critical for choosing
appropriate therapy. TRUS is a more
commonly available imaging method than
MRI/MRSI but it is considered by most
urologists to be an insensitive method for
detecting local extension and predicting
clinical stage. MRI has a reported accuracy of
75–90% for staging prostate cancer [32].
Conventional contrast-enhanced MRI has
provided no significant advantage in locating
cancer within the prostate, or in assessing
extraprostatic spread of cancer, with a
reported NPV of 67–90% and specificity of
47–100%.
Previous histopathological studies have
shown that prostate cancer volume is a
significant predictor of extracapsular spread.
Therefore, tumour volume estimates made on
MRSI findings have been used in conjunction
with high-specificity MRI criteria to diagnose
extracapsular spread, thereby improving
the accuracy of MRI in the diagnosis of
extracapsular spread. Yu et al. [33] showed
that, considering a threshold of 1 mL of
tumour volume per lobe as predictive of
extracapsular spread, adding MRSI increased
the accuracy of MRI from 0.77 to 0.83 in
predicting early spread outside the prostate.
Hricak et al. [34] reported that the surgical
plan should be altered for 39% of the
neurovascular bundles at risk on MRI/MRSI
examination. In cases with known high-risk
disease MRI/MRSI had an even greater effect
where it could help to avoid a wide excision of
the neurovascular bundle in most cases.
STATUS IN DIRECTING TREATMENT BASED
ON THE LOCATION OF PROSTATE CANCER:
EFFECT ON SURGICAL TECHNIQUE,
DIRECTING IMPLANTS FOR
BRACHYTHERAPY/CRYOTHERAPY
The location of tumour was recently related
to the risk of tumour recurrence after
prostatectomy, with a higher risk when the
surgical margins are positive at the base than
at the apex. This could affect the refinements
made in surgical technique to reduce positive
margins and improve overall oncological
outcomes. Preoperative knowledge of tumour
location with MRSI could help the surgeon in
this regard.
In addition, intraglandular localization of
prostate cancer has attained importance with
the emergence of various disease-targeted
therapies, e.g. interstitial brachytherapy,
intensity-modulated radiotherapy and
cryosurgery. Despite various advances
in external beam radiotherapy and
brachytherapy, true optimization of dose
distributions is still not possible because of
uncertainties in tumour position within the
prostate. This uncertainty forces the radiation
oncologist to deliver the maximum dose to
the entire gland, which often results in a
higher than optimum dose to the urethra.
Although urinary side-effects might be
inevitable for patients treated with prostatic
implantation, it is hypothesized that with
improved optimization techniques and
intraoperative correction protocols to further
enhance needle distribution and seed
placement, these side-effects can be reduced
without compromising local control. The
MRS-guided plan has been shown to
successfully allow increased tumour doses
without increasing the maximum urethral
dose [35].
STATUS FOR THE FOLLOW-UP OF
PROSTATE CANCER FOR DETECTING
RECURRENCE
Presently PSA is used to follow patients with
prostate cancer after any type of therapy
(surgery, radiation, hormonal, cryotherapy,
etc.). However, PSA is not specific and levels
might be increased due to residual BPH tissue.
Conventional radiological techniques like
TRUS, CT and MRI have very poor accuracy for
diagnosing and localizing tumour in this
setting, because most therapies cause
changes in the tissue that resemble cancer
tissue on these imaging studies. Biopsy
remains the only definitive means to diagnose
residual disease or recurrence, and it is also
subject to sampling errors. In this regard,
MRSI has been shown to be effective in
differentiating between benign, malignant
and necrotic tissue after surgical, hormonal,
radiation and cryotherapy [9,36–39].
Kurhanewicz et al. [40] used 3D MRSI to
investigate the clinical potential for follow-up
of the response to cryosurgery and showed its
reliability in assessing the presence and the
spatial extent of recurrent local disease after
therapy. Parivar et al. [39] reported that 3D
MRSI was better than TRUS and MRI in
differentiating among prostate cancer, BPH
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and necrosis when local recurrence after
cryosurgery is suspected. Pickett et al. [41]
studied MRI/MRSI before and at varying times
after external beam radiotherapy, and showed
a strong correlation between MRI/MRSI and
biopsy findings, whereas there was a very
weak correlation with PSA levels. This implies
that MRI/MRSI might be useful for detecting
residual/recurrent tumour after radiotherapy.
A complete metabolic atrophy has shown a
NPV of 100% for the presence of local
recurrence.
FUTURE ADVANCES
Clinical MR systems with field strengths ≥3 T
can increase the spatial resolution of the data
acquired, as well as improve chemical-shift
dispersion, thereby reducing the overlap of
metabolites in the proton spectrum. Newer
metabolic markers might be identified which
could provide increased specificity to this
technique.
Other MR-based imaging techniques, like
diffusion-weighted imaging, magnetization
transfer imaging, etc., are being developed
and could be combined with MRI/MRSI to
further improve the accuracy in diagnosis of
cancer prostate [42,43].
SUMMARY
Currently, various studies on MRSI provide
compelling evidence for differentiating
malignant from benign tissue. It can be used
in combination with other studies to improve
various aspects in the management of
prostate cancer. Improving the cancer
detection rate of biopsy, selecting cases for
watchful management or repeat biopsy,
directing probes to the affected part for the
treatment, follow-up after definitive
treatment for detecting recurrence, etc., are
some aspects where MRSI might have a role
in the near future.
CONFLICT OF INTEREST
None declared.
REFERENCES
1
©
Sharma U, Jagannathan NR. Potential of
in vivo Magnetic Resonance Spectroscopy
(MRS) in medicine. Proc Indian Natl Sci
Acad A 2004; 70A: 555–77
2 Costello LC, Franklin RB. Concepts of
citrate production and secretion by
prostate: hormonal relationships in
normal and neoplastic prostate. Prostate
1991; 19: 181–205
3 Costello LC, Franklin RB. The
intermediary metabolism of the prostate:
a key to understanding the pathogenesis
and progression of prostate malignancy.
Oncology 2000; 59: 269–82
4 Cooper JF, Farid I. The role of citric acid
in the physiology of the prostate: lactic/
citrate ratios in benign and malignant
prostatic homogenates as an index of
prostatic malignancy. J Urol 1964; 92:
533–6
5 Rifkin MD. MRI of the prostate. Crit
Rev Diagn Imaging 1990; 31: 223–
62
6 Mazaheri Y, Dave AS, Muellner A,
Hricak H. MR imaging of the prostate in
clinical practice. MAGMA 2008; 21: 379–
92
7 Kurhanewicz J, Vigneron DB, Nelson SJ
et al. Citrate as an in vivo marker to
discriminate prostate cancer from benign
prostatic hyperplasia and normal prostate
peripheral zone: detection via localized
proton spectroscopy. Urology 1995; 45:
459–66
8 Kurhanewicz J, Vigneron DB, Hricak H,
Narayan P, Carroll P, Nelson SJ. Three
dimensional H1 MR spectroscopic
imaging of the in situ human prostate
with high (0.24–0.7 cm3) spatial
resolution. Radiology 1996; 198: 795–
805
9 Parivar F, Hricak H, Shinohar K et al.
Detection of locally recurrent prostate
cancer after cryotherapy: evaluation
by transrectal ultrasound, magnetic
resonance imaging and three dimensional
proton magnetic resonance spectroscopy.
Urology 1996; 48: 594–9
10 Males RG, Vigneron DB, StarLack J
et al. Clinical application of BASING
and spectral/spatial water and lipid
suppression pulses for prostate cancer
staging and localization by in vivo 3D 1H
magnetic resonance spectroscopic
imaging. Magn Reson Med 2000; 43: 17–
22
11 Kumar R, Kumar M, Jagannathan NR,
Gupta NP, Hemal AK. Proton magnetic
resonance spectroscopy with a body coil
in the diagnosis of carcinoma prostate.
Urol Res 2004; 32: 36–40
12 vanDorsten FA, van der Graaf M,
Engelbrecht MR et al. Combined
quantitative dynamic contrast-enhanced
MR imaging and (1)H MR spectroscopic
imaging of human prostate cancer. J
Magn Reson Imaging 2004; 20: 279–87
13 Van der Graaf M, Schipper RG,
Oosterhof GO, Schalken JA, Verhofstad
AA, Heerschap A. Proton MR
spectroscopy of prostatic tissue focused
on the detection of spermine, a possible
biomarker of malignant behavior in
prostate cancer. MAGMA 2000; 10: 153–9
14 Shukla-Dave A, Hricak H, Moskowitz C
et al. Detection of prostate cancer with
MR spectroscopic imaging: an expanded
paradigm incorporating polyamines.
Radiology 2007; 245: 499–506
15 Kurhanewicz J, Vigneron DB, Males RG,
Swanson MG, Yu KK, Hricak H. The
prostate. MR imaging and spectroscopy.
Present Future Radiol Clin North Am 2000;
38: 115–38
16 Sheidler J, Hricak H, Vigneron DB et al.
Prostate cancer: localization with threedimensional proton MR spectroscopic
imaging- clinicopathologic study.
Radiology 1999; 213: 473–80
17 Zakian KL, Eberhardt S, Hricak H
et al. Transition zone prostate cancer:
metabolic characteristics at 1H MR
spectroscopic imaging-initial results.
Radiology 2003; 229: 241–7
18 Fütterer JJ, Scheenen TW, Heijmink SW
et al. Standardized threshold approach
using three-dimensional proton magnetic
resonance spectroscopic imaging in
prostate cancer localization of the entire
prostate. Invest Radiol 2007; 42: 116–22
19 Wefer AE, Hricak H, Vigneron DB et al.
Sextant localization of prostate cancer:
comparison of sextant biopsy, magnetic
resonance imaging and magnetic
resonance spectroscopic imaging with
step section histology. J Urol 2000; 164:
400–5
20 Swanson MG, Vigneron DB, Tabatabai L
et al. Proton HR-MAS spectroscopy and
quantitative pathologic analysis of MRI/
3D- MRSI-targetted postsurgical prostate
tissues. Magn Reson Med 2003; 50: 944–
54
21 Kumar V, Jagannathan NR, Kumar R
et al. 3D 1H MRSI based TRUS guided
biopsies in men with suspected prostate
cancer. Proc Intl Soc Mag Reson Med
2006; 14: 1790
22 Kumar R, Nayyar R, Kumar V et al.
Potential of magnetic resonance
2009 THE AUTHORS
JOURNAL COMPILATION
©
2009 BJU INTERNATIONAL
1619
N AY YA R ET AL.
23
24
25
26
27
28
29
spectroscopic imaging in predicting
absence of prostate cancer in men with
serum prostate-specific antigen between
4 and 10 ng/ml: a follow-up study.
Urology 2008; 72: 859–63
Naughton CK, Smith DS, Humphrey
PA, Catalona WJ, Keetch DW. Clinical
and pathologic tumor characteristics
of prostate cancer as a function of
the number of biopsy cores: a
retrospective study. Urology 1998; 52:
808–13
Rabbani F, Stroumbakis N, Kava BR,
Cookson MS, Fair WR. Incidence and
clinical significance of false negative
sextant prostate biopsies. J Urol 1998;
159: 1247–50
Kumar V, Jagannathan NR, Kumar R
et al. Transrectal ultrasound-guided
biopsy of prostate voxels identified as
suspicious of malignancy on three
dimensional 1H MR spectroscopic
imaging in patients with abnormal
digital rectal examination or raised
prostate specific antigen level of
4–10 ng/ml. NMR Biomed 2007; 20: 11–
20
Coakley FV, Kurhanewicz J, Lu Y
et al. Prostate cancer tumor volume:
measurement with endorectal MR and
MR spectroscopic imaging. Radiology
2002; 223: 91–7
Beyersdorff D, Winkel A, Hamm B, Lenk
S, Loening SA, Taupitz M. MR imaging–
guided prostate biopsy with a closed MR
Unit at 1.5 T: initial results. Radiology
2005; 234: 576–81
Yuen JSP, Thng CH, Tan PH et al.
Endorectal magnetic resonance imaging
and spectroscopy for the detection of
tumor foci in men with prior negative
transrectal ultrasound prostate biopsy.
J Urol 2004; 171: 1482–6
Prando A, Kurhanewicz J, Borges AP,
Oliveira EM Jr, Figueiredo E. Prostatic
biopsy directed with endorectal MR
spectroscopic imaging findings in
patients with elevated prostate specific
antigen levels and prior negative biopsy
1620
30
31
32
33
34
35
36
37
findings: early experience. Radiology
2005; 236: 903–10
Kurhanewicz J, Swanson MG, Nelson
SJ, Vigneron DB. Combined magnetic
resonance imaging and spectroscopic
imaging approach to molecular imaging
of prostate cancer. J Magn Reson Imaging
2002; 16: 451–63
Zakian KL, Sircar K, Hricak H et al.
Correlation of proton MR spectroscopic
imaging with Gleason score based on
step-section pathologic analysis after
radical prostatectomy. Radiology 2005;
234: 804–14
Bartolozzi C, Menchi I, Lencioni R et al.
Local staging of prostate carcinoma with
endorectal coil MRI: correlation with
whole mount radical prostatectomy
specimens. Eur Radiol 1996; 6: 339–
45
Yu KK, Scheidler J, Hricak H, Vigneron
DB, Zaloudek C, Nelson S. Improved
prediction of extracapsular extension in
patients with prostate cancer by the
addition of 3D H1-MR spectroscopic
imaging to MR imaging. Radiology 1999;
213: 481–8
Hricak H. MR imaging and MR
spectroscopic imaging in the pretreatment evaluation of prostate cancer.
Br J Radiol 2005; 78: S103–11
Zaider M, Zelefsky MJ, Lee EK et al.
Treatment planning for prostate implants
using magnetic resonance spectroscopic
imaging. Int J Radiat Oncol Biol Phys
2000; 47: 1085–96
Scharen-Guivek VLM, Males R, Nelson
SJ, Mueller-Lisse UG, Vigneron DB,
Kurhanewicz J. Evaluation of local
prostate recurrence after radical
prostatectomy using magnetic resonance
spectroscopic imaging. Presented at
the Seventh Annual Meeting of The
International Society for Magnetic
Resonance in Medicine, Philadelphia, PA,
1999
Bessette A, Mueller-Lisse UG, Swanson
M et al. Localization of prostate cancer
after hormonal ablation by MRI and 3D
38
39
40
41
42
43
1H- MRSI. Case control study with
pathological correlation. Presented at
the Seventh Annual Meeting of The
International Society for Magnetic
Resonance in Medicine, Philadelphia, PA,
1999; 1519
Males R, Okuno W, Vigneron DB et al.
Monitoring effects of prostate cancer
brachytherapy using combined MRI/MRS.
Presented at the Seventh Annual Meeting
of The International Society for Magnetic
Resonance in Medicine, Philadelphia, PA,
1999
Parivar F, Kurhanewicz J. Detection
of recurrent prostate cancer after
cryosurgery. Curr Opin Urol 1998; 8: 83–6
Kurhanewicz J, Vigneron DB, Hricak H
et al. Prostate cancer: metabolic response
to cryosurgery as detected with 3D H1MR
spectroscopic imaging. Radiology 1996;
200: 489–96
Pickett B, Kurhanewicz J, Coakley F
et al. Use of MRI and spectroscopy in
evaluation of external beam radiotherapy
for prostate cancer. Int J Radiat Oncol Biol
Phys 2004; 60: 1047–55
Kumar V, Jagannathan NR, Kumar R
et al. Correlation between metabolite
ratios and ADC values of prostate in men
with increased PSA level. Magn Reson
Imaging 2006; 24: 541–8
Kumar V, Jagannathan NR, Kumar R
et al. 3D 1H MR spectroscopic imaging
and diffusion weighted imaging of
prostate in men with raised PSA. Eur
Biophys J 2005; 32: 761
Correspondence: Rajeev Kumar, Urology, All
India Institute of Medical Sciences, New Delhi,
India.
e-mail: [email protected]
Abbreviations: MRSI, MR spectroscopic
imaging; NMR, nuclear magnetic resonance;
PZ, peripheral zone; TZ, transition zone;
PPV/NPV, positive/negative predictive value;
RF, radiofrequency; 3D, three-dimensional;
TR, repetition time; TE, echo time; SNR,
signal-to-noise ratio.
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JOURNAL COMPILATION
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2009 BJU INTERNATIONAL