Takahiro Ueda1, Yoshiharu Ohno1,2, Kaori Yamamoto3, Masao Yui3, Masato Ikedo3, Saki Takeda4, Akiyoshi Iwase4, Yuka Oshima1, Nayu Hamabuchi1, Satomu Hanamatsu1, Yuki Obama1, Hiroyuki Nagata1, Hirotaka Ikeda1, Kazuhiro Murayama2, and Hiroshi Toyama1
1Radiology, Fujita Health University School of Medicine, Toyoake, Japan, 2Joint Research Laboratory of Advanced Medical Imaging, Fujita Health University School of Medicine, Toyoake, Japan, 3Canon Medical Systems Corporation, Otawara, Japan, 4Radiology, Fujita Health University Hospital, Toyoake, Japan
Synopsis
We hypothesize that CEST is at least as valuable as DWI and may have a
potential to improve differentiation capability of malignant from benign
prostatic areas as one of the combined quantitative discriminators on prostatic
MR imaging. The purpose of this study
was to compare the capability for distinguishing malignant from benign areas
among CEST, DWIs at standard and super high b values and combined quantitative
discriminator in suspected prostatic cancer patients.
Introduction
Multi-parametric magnetic resonance (MR) imaging is widely used to
detect, localize, and stage prostate cancer.
Currently, diffusion-weighted imaging (DWI) is an integral part of the
multi-parametric MR imaging in the prostatic cancer, and apparent diffusion
coefficient (ADC) maps derived from DWI have not only been shown to detect
prostatic cancer, but also ADC values correlate with the histologic grade of it. However, lesions on ADC maps can be subtle
and it has been observed that inclusion of DWI with high b value improves the
conspicuity of prostatic cancer. Therefore,
the recently published PI-RADS ver. 2 criteria is suggested to obtain DWI with
high b value above 1400 s/mm21.
However, appropriate b value has not been determined in this
setting. In the last several years,
chemical exchange saturation transfer (CEST) imaging at 3.5 ppm (APTw imaging)
has been suggested as one of the MR-based molecular imaging techniques in patients
with lung, rectum, uterus and ovary cancers or tumors2-6. CEST Imaging can be performed on proteins,
amino acids and DNAs including chemical exchangeable protons such as hydroxyl protons (-OH: ~1ppm), amine protons
(-NH2: ~2ppm) and amide protons (R-C(=O)-NH2 or R-C(=O)-NHR1 <R ≠ H>: ~3.5ppm)7, 8. However, no major reports have been evaluated
the capability of APTw imaging for differentiation of malignant from benign
prostatic areas in patients with prostatic cancer. In addition, no one have not determined how
to apply APTw imaging with DWI in this setting. We hypothesize that APTw imaging is at least
as valuable as DWI with super high b value and may have a potential to improve
differentiation capability of malignant from benign prostatic areas as one of
the combined quantitative discriminators on prostatic MR imaging. The purpose of this study was to compare the
capability for distinguishing malignant from benign areas among CEST, DWIs at
standard and super high b values and combined quantitative discriminator in
suspected prostatic cancer patients.Materials and Methods
This study included 60 patients (mean age: 67
years; range=49-80 years) with a mean serum prostate specific antigen (PSA) of
10.2±6.7 ng/mL (range=4.9-87.8 ng/mL) underwent MR
imaging of prostate with CEST imaging by 2D fast advanced spin-echo (FASE)
sequence with MT pulses and DWI with b values at 0, 1500 (DWI1500)
and 3000 (DWI3000) mm2/s by spin-echo (SE) type echo
planar imaging (EPI) sequence, systemic prostate biopsy, radical prostatectomy,
and pathological examination. All
prostatic MR imaging were performed at two 3T MR systems (Vantage Centurian,
Otawara, Japan). According to the
pathological results, 56 areas were determined as malignant, and 56 out of 664
areas were computationally selected as benign.
Magnetization transfer ratio asymmetry (MTRasym) at 3.5 ppm,
ADCs from DWI1500 (ADC1500) and DWI3000 (ADC3000)
in each area were determined by ROI measurements. To compare each quantitative index between
malignant and benign prostatic areas, Student’s t-test was performed. Then, multivariate regression analysis was
performed to investigate the discriminating factors for distinguishing
malignant from benign prostatic areas.
ROC analysis was performed to compare differentiation capability among
all indexes as well as combine discriminators.
Diagnostic performance was compared among all methods by ROC
analysis. Finally, sensitivity,
specificity and accuracy were compared among all methods by McNemar’s test. A p value less than 0.05 was considered as significant in this
study. Results
Representative cases are shown in Figures 1. Comparison of each quantitative index between
malignant and benign prostatic areas is shown in Figure 2. There were
significant differences of all indexes between two areas (p<0.05). Multiple regression analysis was revealed
that ADC3000 (Odds ratio: 0.00003, p<0.0001) and MTRasym
at 3.5ppm (Odds ratio: 1.01, p=0.007) as discriminators. Results of ROC
analysis and diagnostic performance among all quantitative indexes and combined
discriminators are shown in Figure 3. Area under the curve (AUC), specificity
and accuracy of ADC3000 were significantly larger or higher than
those of ADC1500 (p<0.05).
AUC, sensitivity and accuracy of combined discriminators were
significantly larger or higher than those of ADC1500, ADC3000
and MTRasym at 3.5ppm (p<0.05). Conclusion
CEST
is considered as valuable as DWIs at b value as 1500 and 3000mm2/s and
would be better to be combined with DWI3000 for distinguishing
malignant from benign areas in suspected prostatic cancer patients. Acknowledgements
This study was technically and financially supported by Canon Medical Systems Corporation. References
- Purysko AS, Baroni RH, Giganti F, et al. PI-RADS Version
2.1: A Critical Review, From the AJR Special Series on Radiology Reporting and
Data Systems. AJR Am J Roentgenol. 2021; 216(1): 20-32.
- Ohno Y, Yui M, Koyama H, et al. Chemical Exchange
Saturation Transfer MR Imaging: Preliminary Results for Differentiation of
Malignant and Benign Thoracic Lesions. Radiology. 2016; 279(2): 578-589.
- Ohno Y, Kishida Y, Seki S, et al. Amide proton
transfer-weighted imaging to differentiate malignant from benign pulmonary
lesions: Comparison with diffusion-weighted imaging and FDG-PET/CT. J Magn
Reson Imaging. 2018; 47(4): 1013-1021.
- Takayama Y, Nishie A, Togao O, et al. Amide Proton
Transfer MR Imaging of Endometrioid Endometrial Adenocarcinoma: Association
with Histologic Grade. Radiology. 2018; 286(3): 909-917.
- Nishie A, Takayama Y, Asayama Y, et al. Amide proton
transfer imaging can predict tumor grade in rectal cancer. Magn Reson Imaging.
2018; 51: 96-103.
- Ishimatsu K, Nishie A, Takayama Y, et al. Amide proton
transfer imaging for differentiating benign ovarian cystic lesions: Potential
of first time right. Eur J Radiol. 2019; 120: 108656.
- van Zijl PC, Yadav NN. Chemical exchange saturation
transfer (CEST): what is in a name and what isn't? Magn Reson Med. 2011
Apr;65(4):927-48.
- Zhou J, Heo HY, Knutsson L, van Zijl PCM, Jiang S. APT-weighted
MRI: Techniques, current neuro applications, and challenging issues. J Magn
Reson Imaging. 2019; 50(2): 347-364.