Anne Adlung1, Fabian Tollens2, Nadia Karina Paschke1, Jennifer Hümsch1, Niklas Westhoff3, Daniel Hausmann2,4, Lothar Rudi Schad1, Dominik Nörenberg2, and Frank Gerrit Zöllner1,5
1Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, 2Department of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, 3Department of Urology and Urosurgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, 4Department of Radiology, Kantonspital Baden, Baden, Switzerland, 5Mannheim Institute for Intelligent System in Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Synopsis
Prostate cancer is the most common tumor in men. 23Na-MRI provides
complementary information to multiparametric-MRI. Tissue sodium concentration (TSC)
quantification depends on sodium references-usually external phantoms.
This study investigates TSC-quantification based on internal references
(iliac-artery).
23Na-MRI of 19 male
patients with suspected PCa was included. TSC in the prostate was quantified
based on external reference vials and based on the iliac artery.
Three patients showed a PI-RADs-5 lesion and had an elevated TSC which is
in alignment with prvious studies. No significant differences between both methods were found in the whole prostate.
Internal references for TSC quantification could simplify
23Na-MRI.
Introduction
Prostate cancer (PCa) is the most commonly diagnosed tumor and second
leading cancer-related cause of death in men worldwide[1-3]. Multiparametric-MRI (mpMRI) according to the
established PI-RADS guidelines is of high value for the PCa detection[4]. On T2-weighted MRI, PCa is commonly depicted
as low-signal-intensity region[5,6]. Combining different MRI techniques leads to
higher accuracy for the PCa detection[7-9]. However, diagnostic accuracy is affected by
benign diseases and cancer-mimics such as prostatitis or atypical BPH nodules
which may express similar appearances on MRIs[10].
Quantitative 23Na-MRI and the resulting tissue sodium
concentration (TSC) can provide information about cell vitality and activity[11,12]. Previous studies have shown an increase in
TSC within various tumors and correlations between TSC and tumor malignancies[13-15]. Therefore, 23Na-MRI has the
potential to become a biomarker for prostate cancer diagnosis and
characterization of tumor aggressiveness providing complementary information to
existing mpMRI[10,16-18].
To achieve this, precise TSC quantification is crucial and requires references
with a known sodium concentration. Positioning of reference phantoms within the
field of view (FoV) is well established but quantification accuracy decreases
with an increasing distance to the region of interest (ROI) such as the
prostate. Thus, internal 23Na references are warranted. TSC within the
human blood shows little
individual variation[19,20] and is around 85mM which points
towards the usage of periprostatic blood vessels as references located close to
the ROI.
The study compares two different methods for TSC quantification within
the prostatic tissue based on external (method1) and internal (method2)
references. Methods
We prospectively included 22 male patients with clinically suspected PCa.
Data acquisition was successful for 19 patients (66.1±7.0 years).
Each patient underwent a standard mpMRI of the prostate according to the
ACR PI-RADS guidelines[21] at 3T (Magnetom Skyra, Siemens Healthcare GmbH, Erlangen,
Germany). In addition, the coil was changed to a dual-tuned-1H/23Na
16-channel body-coil (Rapid Biomedical, Rimpar, Germany) and the study protocol
followed comprising a 23Na 3D-radial density-adapted sequence[22] (Table1). The reference amplitude was
optimized for each patient individually based on calibrations performed prior
to the sequence. A 1H-2D-Turbo-Spin-Echo (TSE) (Table 1) was acquired
with the dual-tuned coil for optimal image co-registration. During the
measurements, four reference phantoms (2x50mM, 2x100mM NaCl, 4% Agarose each, ∅=25mm) were
positioned on both sides of the patient.
The acquired 23Na-MRI was reconstructed offline in MATLAB
2018a (Mathworks Inc., Natick, MA, USA). The B1-inhomogeneities were corrected
with a scan of a homogenous phantom filled with a saline solution resulting in
a correction factor for each image voxel within the phantom region.
Image co-registration of the 23Na-MRI to the T2w-MRI was
performed in MATLAB by resampling the 23Na-MRI to the T2w resolution
and slice positioning alignment. Segmentation of the prostate into its transitional
zone (TZ) and peripheral zone (PZ) was performed in MITK (German Cancer
Research Center, Heidelberg, Germany) by a radiologist on the T2w-MRI (Figure 1-A).
Two different methods for the TSC quantification were applied:
1.Quantification
based on the external reference phantoms
2.Quantification
based on internal reference (iliac arteries).
For both methods, volumes of interest (VOIs) were defined within the 23Na-MRI
and a linear fit was performed based on its mean signal-intensity. For the
first method, quantification was performed on the original 23Na-MRI
after the B1-correction (Figure 1-B). The second quantification method was
performed after B1-correction and image co-registration to the T2w-TSE for a
more precise view of the iliac vessels (Figure 1-C). Results
All 19 patients showed a mean TSC of 35.8±5.7mM (method1) versus 35.7±6.1mM (method2) in the whole prostate and mean difference between both
quantification methods was 4.6±2.7mM, with no statistically significant
difference (p=0.95); Table 2. Figure 2 depicts the Bland Altman plot comparing
both methods.
Two of the examined patients had a PI-RADS 5 lesion in the TZ with a
mean TSC of 40.8mM and 37.3mM (method1) and 40.5mM and 39.3mM (method2). One
patient showed a PI-RADS 5 lesion within the PZ (43.3±10.4mM and 36.7±7.5mM).
The remaining 16 patients had no lesions or lower rated ones. TSC in patients
with PCa was higher than mean TSC of all patients within the method and
anatomical region, Figure 3.Discussion
In this study we investigated whether 23Na quantification in
the human prostate is affected by the choice of an internal (e.g. iliac arteries)
versus the commonly used external references. The mean TSC difference within
the whole prostate is below 5mM between both quantification methods, which is
within the standard deviation of the study population.
The results of both methods are in alignment with previously published
results from Barrett et al.[16,17].
Particularly the results within the patients with PI-RADS 5 lesion are
promising, considering the fact that an elevated TSC was found within the
affected region with both methods pointing towards an elevated TSC within
malignant lesions.
The internal reference could be used as an alternative to external vials.
However, correlations with the individuals‘ blood sodium concentrations could
facilitate the validation of sodium levels in future investigations.Conclusion
The study shows that using internal references for TSC quantification
in the human prostate is feasible and results are similar to those of
external references and literature. This might simplify the application
of 23Na-MRI in future clinical research as correct positioning of
external references would become obsolete.Acknowledgements
This research project is partly supported of the
Research Campus M2OLIE funded by the German Federal Ministry of Education and
Research (BMBF) within the Framework “Forschungscampus: public-private
partnership for Innovations” under the funding code 13GW0388A.References
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