IMAGING

Detection of prostate cancer with MR spectroscopic imaging: an expanded paradigm incorporating polyamines
Shukla-Dave A, Hricak H, Moskowitz C, Ishill N, Akin O, Kuroiwa K, Spector J, Kumar M, Reuter VE, Koutcher JA, Zakian KL
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Radiology. 2007; 245: 499-506

• Purpose: To characterize benign and malignant prostate peripheral zone (PZ) tissue retrospectively by using a commercial magnetic resonance (MR) spectroscopic imaging package and incorporating the choline plus creatine-to-citrate ratio ([Cho + Cr]/Cit) and polyamine (PA) information into a statistically based voxel classification procedure.
• Materials and Methods: The institutional review board approved this HIPAA-compliant study and waived the requirement for informed consent. Fifty men (median age, 60 years; range, 44-69 years) with untreated biopsy-proved prostate cancer underwent combined endorectal MR imaging and MR spectroscopic imaging. Commercial software was used to acquire and process MR spectroscopic imaging data. The (Cho + Cr)/Cit and the PA level were tabulated for each voxel. The PA level was scored on a scale of 0 (PA undetectable) to 2 (PA peak as high as or higher than Cho peak). Whole-mount step-section histopathologic analysis constituted the reference standard. Classification and regression tree analysis in a training set generated a decision-making tree (rule) for classifying voxels as malignant or benign, which was validated in a test set. Receiver operating characteristic and generalized estimating equation regression analyses were used to assess accuracy and sensitivity, respectively.
• Results: The median (Cho + Cr)/Cit was 0.55 (mean +/- standard deviation, 0.59 +/- 0.03) in benign and 0.77 (mean, 1.08 +/- 0.20) in malignant PZ voxels (P = .027). A significantly higher percentage of benign (compared with malignant) voxels had higher PA than choline peaks (P < .001). In the 24-patient training set (584 voxels), the rule yielded 54% sensitivity and 91% specificity for cancer detection; in the 26-patient test set (667 voxels), it yielded 42% sensitivity and 85% specificity. The percentage of cancer in the voxel at histopathologic analysis correlated positively (P < .001) with the sensitivity of the classification and regression tree rule, which was 75% in voxels with more than 90% malignancy.
• Conclusion: The statistically based classification rule developed indicated that PAs have an important role in the detection of PZ prostate cancer. With commercial software, this method can be applied in clinical settings.
  
  
• Editorial Comment
  The ratio of choline and creatine to citrate (Cho+Cr/Cit), is the parameter for the detection of prostate cancer on MR spectroscopic imaging (MRSI). As we know this ratio is increased in prostate cancer due to the elevation of choline (high turnover of phospho-lipid in cell membranes of the proliferating tissue) and reduction in the level of citrate (converted to a citrate-oxidating metabolism).Although there is no consensus, voxels are considered very suggestive of cancer if the ratio of choline and creatine to citrate is more than 3 standard deviations above the average ratio (1). However, using these criteria false positive results occurs due to prostatitis and prostatic atrophy. The authors of this meticulous and well-performed prospective study offers additional data regarding the possible role of another metabolite (polyamine) which may help increase the accuracy for the detection of prostate cancer by MRSI. When the polyamine peak is higher or at the same level of the peak of choline and the ratio of Cho+Cr / Cit is above 1.1, the voxel should be considered malignant. However if the ratio is below 1.1 the voxel should be considered benign. As suggested by the authors we already started to apply this method in clinical settings particularly for the detection of prostate cancer in patients with negative biopsies (at least 2) and elevated PSA. In the near future, we will present our preliminary results of this prospective study. It would be interesting to see if this expanded paradigm will be useful to avoid false positive results with MRSI of the prostate. Other prospective studies from different institutions in similar or distinct clinical settings are warranted.

References
1. Males RG, Vigneron DB, Star-Lack J, Falbo SC, Nelson SJ, Hricak H, 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.

Dr. Adilson Prando
Chief, Department of Radiology and
Diagnostic Imaging
Vera Cruz Hospital
Campinas, São Paulo, Brazil
E-mail: aprando@mpc.com.br