Thiele Kobus

Prostate Cancer Aggressiveness: In Vivo Assessment of MR Spectroscopy and Diffusion-weighted Imaging at 3 T

PURPOSE To determine the individual and combined performance of magnetic resonance (MR) spectroscopic imaging and diffusion-weighted (DW) imaging at 3 T in the in vivo assessment of prostate cancer aggressiveness by using histopathologically defined regions of interest on radical prostatectomy specimens to define the prostate cancer regions to be investigated. MATERIALS AND METHODS The local institutional ethics review board approved this retrospective study and waived the informed consent requirement. Fifty-four patients with biopsy-proved prostate cancer underwent clinical MR spectroscopic imaging followed by prostatectomy. Guided by the histopathologic map, all spectroscopy voxels that contained tumor tissue were selected, and metabolite ratios (choline [Cho] plus creatine [Cr]-to-citrate [Cit] and Cho/Cr ratios) were derived. For each spectroscopic voxel, 25th percentile apparent diffusion coefficient (ADC) of the region corresponding to that voxel was determined, representing the most aberrant tumor part on the ADC map, which was often smaller than spectroscopic imaging voxels. Maximum metabolic ratios and minimum 25th percentile ADC of each tumor were related to tumor aggressiveness and were used to differentiate aggressiveness classes. A logistic regression model (LRM) was used to combine data from both modalities. RESULTS Significant correlation was found between aggressiveness classes and maximum Cho+Cr/Cit ratio (ρ=0.36), maximum Cho/Cr ratio (ρ=0.35), and minimum 25th percentile ADC (ρ=-0.63) in the peripheral zone (PZ). In the transition zone (TZ), the correlation was significant for only Cho+Cr/Cit and Cho/Cr ratios (ρ=0.58 and ρ=0.60, respectively). For differentiation between aggressiveness classes, LRM use did not result in significantly improved differentiation over any individual variables. CONCLUSION These findings enabled confirmation that MR spectroscopic imaging and DW imaging offer potential for in vivo noninvasive assessment of prostate cancer aggressiveness, and both modalities have comparable performance. The combination did not result in better performance. Nonetheless, the better performances of metabolite ratios in the TZ and of ADCs in the PZ suggest that they have complementary value.

Assessment of Prostate Cancer Aggressiveness Using Dynamic Contrast-enhanced Magnetic Resonance Imaging at 3 T

BACKGROUND A challenge in the diagnosis of prostate cancer (PCa) is the accurate assessment of aggressiveness. OBJECTIVE To validate the performance of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate at 3 tesla (T) for the assessment of PCa aggressiveness, with prostatectomy specimens as the reference standard. DESIGN, SETTINGS, AND PARTICIPANTS A total of 45 patients with PCa scheduled for prostatectomy were included. This study was approved by the institutional review board; the need for informed consent was waived. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Subjects underwent a clinical MRI protocol including DCE-MRI. Blinded to DCE-images, PCa was indicated on T2-weighted images based on histopathology results from prostatectomy specimens with the use of anatomical landmarks for the precise localization of the tumor. PCa was classified as low-, intermediate-, or high-grade, according to Gleason score. DCE-images were used as an overlay on T2-weighted images; mean and quartile values from semi-quantitative and pharmacokinetic model parameters were extracted per tumor region. Statistical analysis included Spearmans ρ, the Kruskal-Wallis test, and a receiver operating characteristics (ROC) analysis. RESULTS AND LIMITATIONS Significant differences were seen for the mean and 75th percentile (p75) values of wash-in (p = 0.024 and p = 0.017, respectively), mean wash-out (p = 0.044), and p75 of transfer constant (K(trans)) (p = 0.035), all between low-grade and high-grade PCa in the peripheral zone. ROC analysis revealed the best discriminating performance between low-grade versus intermediate-grade plus high-grade PCa in the peripheral zone for p75 of wash-in, K(trans), and rate constant (Kep) (area under the curve: 0.72). Due to a limited number of tumors in the transition zone, a definitive conclusion for this region of the prostate could not be drawn. CONCLUSIONS Quantitative parameters (K(trans) and Kep) and semi-quantitative parameters (wash-in and wash-out) derived from DCE-MRI at 3 T have the potential to assess the aggressiveness of PCa in the peripheral zone. P75 of wash-in, K(trans), and Kep offer the best possibility to discriminate low-grade from intermediate-grade plus high-grade PCa.

In vivo assessment of prostate cancer aggressiveness using magnetic resonance spectroscopic imaging at 3 T with an endorectal coil

BACKGROUND One of the most important clinical challenges in prostate cancer (PCa) management is an in vivo assessment of cancer aggressiveness. OBJECTIVE To validate the performance of magnetic resonance (MR) spectroscopic imaging (MRSI) of the prostate at 3 T for the purpose of assessing tumour aggressiveness based on the ratio of choline plus creatine to citrate (Cho+Cr/Cit) and of choline to creatine (Cho/Cr), using the Gleason score of the radical prostatectomy (RP) specimen as the gold standard. DESIGN, SETTING, AND PARTICIPANTS A total of 43 biopsy-proven PCa patients with 53 clinically relevant tumour foci were retrospectively included in this study. MEASUREMENTS Patients underwent MR imaging and MRSI examination followed by RP. From MRSI, all spectroscopy voxels containing tumour were selected by a radiologist guided by the prostatectomy histopathology map only. For each tumour, two spectroscopists determined the maximum Cho+Cr/Cit, Cho/Cr, and malignancy rating using a standardised threshold approach, incorporating both metabolic ratios. The maximum Cho+Cr/Cit, Cho/Cr, and malignancy ratings showed a relation to tumour aggressiveness and so were used to differentiate among tumour aggressiveness classes. RESULTS AND LIMITATIONS The maximum Cho+Cr/Cit ratio, maximum Cho/Cr ratio, and malignancy rating of a standardised threshold approach separated low-grade from higher-grade tumours, with areas under the receiver operating characteristic (ROC) curves of 0.70, 0.74, and 0.78, respectively. CONCLUSIONS MRSI offers possibilities for an in vivo, noninvasive assessment of PCa aggressiveness. The combination of the different metabolite ratios was used with promising results for discrimination among different aggressiveness classes.

Multiparametric Magnetic Resonance Imaging for Discriminating Low-Grade From High-Grade Prostate Cancer.

ObjectiveThe aim of this study was to determine and validate the optimal combination of parameters derived from 3-T diffusion-weighted imaging, dynamic contrast-enhanced imaging, and magnetic resonance (MR) spectroscopic imaging for discriminating low-grade from high-grade prostate cancer (PCa). Materials and MethodsThe study was approved by the institutional review board, and the need for informed consent was waived. Ninety-four patients with PCa who had undergone multiparametric MR imaging (MRI) before prostatectomy were included. Cancer was indicated on T2-weighted images, blinded to any functional data, with prostatectomy specimens as the reference standard. Tumors were classified as low grade or high grade based on Gleason score; peripheral zone (PZ) and transition zone (TZ) tumors were analyzed separately. In a development set (43 patients), the optimal combination of multiparametric MRI parameters was determined using logistic regression modeling. Subsequently, this combination was evaluated in a separate validation set (51 patients). ResultsIn the PZ, the 25th percentile of apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging and washout (WO25) derived from dynamic contrast-enhanced MRI offered the optimal combination of parameters. In the TZ, WO25 and the choline over spermine + creatine ratio (C/SC) derived from MR spectroscopic imaging showed the highest discriminating performance. Using the models built with the development set, 48 (74%) of 65 cancer lesions were classified correctly in the validation set. ConclusionsMultiparametric MRI is a useful tool for the discrimination between low-grade and high-grade PCa and performs better than any individual functional parameter in both the PZ and TZ. The 25th percentile of ADC + WO25 offered the optimal combination in the PZ, and the choline over spermine + creatine ratio + WO25 offered the optimal combination in the TZ. The ADC parameter has no additional value for the assessment of PCa aggressiveness in the TZ.

In vivo 31P MR spectroscopic imaging of the human prostate at 7 T: Safety and feasibility

31P MR spectroscopic imaging of the human prostate provides information about phosphorylated metabolites that could be used for prostate cancer characterization. The sensitivity of a magnetic field strength of 7 T might enable 3D 31P MR spectroscopic imaging with relevant spatial resolution in a clinically acceptable measurement time. To this end, a 31P endorectal coil was developed and combined with an eight‐channel 1H body‐array coil to relate metabolic information to anatomical location. An extensive safety validation was performed to evaluate the specific absorption rate, the radiofrequency field distribution, and the temperature distribution of both coils. This validation consisted of detailed Finite Integration Technique simulations, confirmed by MR thermometry and B  1+ measurements in a phantom and in vivo temperature measurements. The safety studies demonstrated that the presence of the 31P endorectal coil had no influence on the specific absorption rate levels and temperature distribution of the external eight‐channel 1H array coil. To stay within a 10 g averaged local specific absorption rate of 10 W/kg, a maximum time‐averaged input power of 33 W for the 1H array coil was allowed. For transmitting with the 31P endorectal coil, our safety limit of less than 1°C temperature increase in vivo during a 15‐min MR spectroscopic imaging experiment was reached at a time‐averaged input power of 1.9 W. With this power setting, a second in vivo measurement was performed on a healthy volunteer. Using adiabatic excitation, 3D 31P MR spectroscopic imaging produced spectra from the entire prostate in 18 min with a spatial resolution of 4 cm3. The spectral resolution enabled the separate detection of phosphocholine, phosphoethanolamine, inorganic phosphate, and other metabolites that could play an important role in the characterization of prostate cancer. Magn Reson Med, 2012.

Feasibility of T2 -weighted turbo spin echo imaging of the human prostate at 7 tesla.

To demonstrate that high quality T2‐weighted (T2w) turbo spin‐echo (TSE) imaging of the complete prostate can be achieved routinely and within safety limits at 7 T, using an external transceive body array coil only.

Metabolite ratios in 1H MR spectroscopic imaging of the prostate

In 1H MR spectroscopic imaging (1H‐MRSI) of the prostate the spatial distribution of the signal levels of the metabolites choline, creatine, polyamines, and citrate are assessed. The ratio of choline (plus spermine as the main polyamine) plus creatine over citrate [(Cho+(Spm+)Cr)/Cit] is derived from these metabolites and is used as a marker for the presence of prostate cancer. In this review, the factors that are of importance for the metabolite ratio are discussed. This is relevant, because the appearance of the metabolites in the spectrum depends not only on the underlying anatomy, metabolism, and physiology of the tissue, but also on acquisition parameters. These parameters influence especially the spectral shapes of citrate and spermine resonances, and consequently, the (Cho+(Spm+)Cr)/Cit ratio. Both qualitative and quantitative approaches can be used for the evaluation of 1H‐MRSI spectra of the prostate. For the quantitative approach, the (Cho+(Spm+)Cr)/Cit ratio can be determined by integration or by a fit based on model signals. Using the latter, the influence of the acquisition parameters on citrate can be taken into account. The strong overlap between the choline, creatine, and spermine resonances complicates fitting of the individual metabolites. This overlap and (unknown, possibly tissue‐related) variations in T1, T2, and J‐modulation hamper the application of corrections needed for a “normalized” (Cho+(Spm+)Cr)/Cit ratio that would enable comparison of spectra measured with different prostate MR spectroscopy protocols. Quantitative (Cho+(Spm+)Cr)/Cit thresholds for the evaluation of prostate cancer are therefore commonly established per institution or per protocol. However, if the same acquisition and postprocessing protocol were used, the ratio and the thresholds would be institution‐independent, promoting the clinical usability of prostate 1H‐MRSI. Magn Reson Med 73:1–12, 2015.

(31) P MR spectroscopic imaging of the human prostate at 7 T: T1 relaxation times, Nuclear Overhauser Effect, and spectral characterization

Optimization of phosphorus (31P) MR spectroscopic imaging (MRSI) of the human prostate at 7 T by the evaluation of T1 relaxation times and the Nuclear Overhauser Effect (NOE) of phosphorus‐containing metabolites.

Mapping of prostate cancer by 1H MRSI.

In many studies, it has been demonstrated that 1H MRSI of the human prostate has great potential to aid prostate cancer management, e.g. in the detection and localisation of cancer foci in the prostate or in the assessment of its aggressiveness. It is particularly powerful in combination with T2‐weighted MRI. Nevertheless, the technique is currently mainly used in a research setting. This review provides an overview of the state‐of‐the‐art of three‐dimensional MRSI, including the specific hardware required, dedicated data acquisition sequences and information on the spectral content with background on the MR‐visible metabolites. In clinical practice, it is important that relevant MRSI results become available rapidly, reliably and in an easy digestible way. However, this functionality is currently not fully available for prostate MRSI, which is a major obstacle for routine use by inexperienced clinicians. Routine use requires more automation in the processing of raw data than is currently available. Therefore, we pay specific attention in this review on the status and prospects of the automated handling of prostate MRSI data, including quality control. The clinical potential of three‐dimensional MRSI of the prostate is illustrated with literature examples on prostate cancer detection, its localisation in the prostate, its role in the assessment of cancer aggressiveness and in the selection and monitoring of therapy. Copyright

Phosphorus Magnetic Resonance Spectroscopic Imaging at 7 T in Patients With Prostate Cancer

ObjectivesThe aim of this study was to identify characteristics of phosphorus (31P) spectra of the human prostate and to investigate changes of individual phospholipid metabolites in prostate cancer through in vivo 31P magnetic resonance spectroscopic imaging (MRSI) at 7 T. Materials and MethodsIn this institutional review board–approved study, 15 patients with biopsy-proven prostate cancer underwent T2-weighted magnetic resonance imaging and 3-dimensional 31P MRSI at 7 T. Voxels were selected at the tumor location, in normal-appearing peripheral zone tissue, normal-appearing transition zone tissue, and in the base of the prostate close to the seminal vesicles. Phosphorus metabolite ratios were determined and compared between tissue types. ResultsSignals of phosphoethanolamine (PE) and phosphocholine (PC) were present and well resolved in most 31P spectra in the prostate. Glycerophosphocholine signals were observable in 43% of the voxels in malignant tissue, but in only 10% of the voxels in normal-appearing tissue away from the seminal vesicles. In many spectra, independent of tissue type, 2 peaks resonated in the chemical shift range of inorganic phosphate, possibly representing 2 separate pH compartments. The PC/PE ratio in the seminal vesicles was highly elevated compared with the prostate in 5 patients. A considerable overlap of 31P metabolite ratios was found between prostate cancer and normal-appearing prostate tissue, preventing direct discrimination of these tissues. The only 2 patients with high Gleason scores tumors (≥4+5) presented with high PC and glycerophosphocholine levels in their cancer lesions. ConclusionsPhosphorus MRSI at 7 T shows distinct features of phospholipid metabolites in the prostate gland and its surrounding structures. In this exploratory study, no differences in 31P metabolite ratios were observed between prostate cancer and normal-appearing prostate tissue possibly because of the partial volume effects of small tumor foci in large MRSI voxels.