Multiplet resonances in MRS data from normal and cancerous prostate - Signal Processing in MRS with Biomedical Applications - page 337

Their study [438] was carried out among seven healthy men with normal
prostate and one man with benign prostatic hypertrophy. However, it should
be recalled that while 2D MRS is frequently helpful in identifying overlapping
peaks, attempts to extend 1D fitting algorithms to 2D MRS are virtually
unfeasible [439]. Thus, these data from in vivo 2D MRS have provided es
sentially only qualitative information, due to reliance upon the Fourierbased
signal processing.
A larger number of studies have been performed using in vitro MRS in the
area of prostate cancer diagnostics. Smith et al. [341] compared biopsies from
66 patients with BPH and 21 with prostate cancer. They used multivariate
analysis with a training set and then a test set, achieving 100% sensitivity and
95.5% specificity. The most discriminatory regions were centered on 3.49 ppm
(taurine), 3.43 ppm, 2.53 ppm (citrate), 2.17 ppm, 1.87 ppm (glutamate), and
1.15 ppm. In addition, these authors were able to distinguish the two types
of BPH (glandular and stromal), which require different therapy, on the basis
of much higher citrate in the former.
In marked contrast to the usual basis for diagnosing prostate cancer by in
vivo MRS, Swindle et al. [440] found in their study of 77 prostate specimens
from the prostate, “depleted citrate and elevated choline levels alone were not
accurate markers of malignancy, since citrate levels remain high when a small
amount of malignant disease is present” (p. 144). On the other hand, they
found that lipid, creatine and lysine were helpful. Cancerous prostate tissue
showed a significantly higher lipid to lysine ratio (1.3:1.7) compared to stromal
BPH. Compared to glandular BPH, the lipid to citrate ratio (1.3:2.5) was
significantly higher in malignant prostate. They also found that spermine and
spermidine (3.1 ppm) decreased with increased adenocarcinoma involvement.
Although the cholinecreatine ratio and lipidlysine ratio were significantly
higher in malignant prostate specimens compared to benign prostate tissue,
there was “considerable overlap of ratios, resulting in poor separation of BPH
from cancer” (p. 147). On the other hand, prostate cancers and prostate
intraepithelial neoplasia that were missed with routine histological exam,
but found with histological stepslice analysis were correctly identified using
in vitro MRS.
As noted, the normal prostate accumulates and secretes very high amounts
of citrate. As well as in malignancy, citrate is also low with postbiopsy
hemorrhage, prostatitis, and with therapy. Evaluation of citrate via MRSI
is found to be helpful for following the progression or regression of prostate
cancer after therapy. Costello et al. [416] propose that malignant transforma
tion of prostate cells is associated with citrate oxidation, as opposed to citrate
accumulation. Zinc also accumulates at very high levels in normal prostate
cells; these authors note a relationship among citrate oxidation, loss of zinc
and prostate cancer.
In a review of in vitro studies of prostate cancer through 2000, Koutcher
and colleagues [441] consider that membrane structure may be important
vis-a-vis spectroscopic findings for choline and related compounds that are