Imaging Hyperpolarized Pyruvate and Lactate after Blood-Brain Barrier Disruption with Focused Ultrasound.

Imaging of hyperpolarized 13C-labeled substrates has emerged as an important magnetic resonance (MR) technique to study metabolic pathways in real time in vivo. Even though this technique has found its way to clinical trials, in vivo dynamic nuclear polarization is still mostly applied in preclinical models. Its tremendous increase in signal-to-noise ratio (SNR) overcomes the intrinsically low MR sensitivity of the 13C nucleus and allows real-time metabolic imaging in small structures like the mouse brain. However, applications in brain research are limited as delivery of hyperpolarized compounds is restrained by the blood-brain barrier (BBB). A local noninvasive disruption of the BBB could facilitate delivery of hyperpolarized substrates and create opportunities to study metabolic pathways in the brain that are generally not within reach. In this work, we designed a setup to apply BBB disruption in the mouse brain by MR-guided focused ultrasound (FUS) prior to MR imaging of 13C-enriched hyperpolarized [1-13C]-pyruvate and its conversion to [1-13C]-lactate. To overcome partial volume issues, we optimized a fast multigradient-echo imaging method (temporal resolution of 2.4 s) with an in-plane spatial resolution of 1.6 × 1.6 mm2, without the need of processing large amounts of spectroscopic data. We demonstrated the feasibility to apply 13C imaging in less than 1 h after FUS treatment and showed a locally disrupted BBB during the time window of the whole experiment. From detected hyperpolarized pyruvate and lactate signals in both FUS-treated and untreated mice, we conclude that even at high spatial resolution, signals from the blood compartment dominate in the 13C images, leaving the interpretation of hyperpolarized signals in the mouse brain challenging.

Simple and broadly applicable automatic quality control for 3D 1 H MR spectroscopic imaging data of the prostate.

PURPOSE: Quality control (QC) is a prerequisite for clinical MR spectroscopic imaging (MRSI) to avoid that bad spectra hamper data interpretation. The aim of this work was to present a simple automatic QC for prostate 1 H MRSI that can handle data obtained with different commonly used pulse sequences, echo times, field strengths, and MR platforms. METHODS: A QC method was developed with a ratio (Qratio) where the numerator and the denominator are functions of several signal heights, logically combined for their positive or negative contribution to spectral quality. This Qratio was tested on 4 data sets obtained at 1.5, 3, and 7T, with and without endorectal coil and different localization sequences and echo times. Spectra of 25,248 voxels in 26 prostates were labeled as acceptable or unacceptable by MRS experts as gold standard. A threshold value was determined for Qratio from a subset of voxels, labeled in consensus by 4 experts, for an optimal accuracy to separate spectra. RESULTS: Applying this Qratio threshold to the remaining test voxels, an automatic separation of good and bad spectra was possible with an accuracy of 0.88, similar to manual separation between the 2 classes. Qratio values were used to generate maps representing spectral quality on a binary or continuous scale. CONCLUSION: Automated QC of prostate 1 H MRSI by Qratio is fast, simple, easily transferable and more practical than supervised feature extraction methods and therefore easy to integrate into different clinical MR systems. Moreover, quality maps can be generated to read the reliability of spectra in each voxel.

Evaluation of fitting models for prostate tissue characterization using extended-range b-factor diffusion-weighted imaging.

PURPOSE: To compare the fitting and tissue discrimination performance of biexponential, kurtosis, stretched exponential, and gamma distribution models for high b-factor diffusion-weighted images in prostate cancer. METHODS: Diffusion-weighted images with 15 b-factors ranging from b = 0 to 3500 s/mm2 were obtained in 62 prostate cancer patients. Pixel-wise signal decay fits for each model were evaluated with the Akaike Information Criterion (AIC). Parameter values for each model were determined within normal prostate and the index lesion. Their potential to differentiate normal from cancerous tissue was investigated through receiver operating characteristic analysis and comparison with Gleason score. RESULTS: The biexponential slow diffusion fraction fslow , the apparent kurtosis diffusion coefficient ADCK , and the excess kurtosis factor K differ significantly among normal peripheral zone (PZ), normal transition zone (TZ), tumor PZ, and tumor TZ. Biexponential and gamma distribution models result in the lowest AIC, indicating a superior fit. Maximum areas under the curve (AUCs) of all models ranged from 0.93 to 0.96 for the PZ and from 0.95 to 0.97 for the TZ. Similar AUCs also result from the apparent diffusion coefficient (ADC) of a monoexponential fit to a b-factor sub-range up to 1250 s/mm2 . For kurtosis and stretched exponential models, single parameters yield the highest AUCs, whereas for the biexponential and gamma distribution models, linear combinations of parameters produce the highest AUCs. Parameters with high AUC show a trend in differentiating low from high Gleason score, whereas parameters with low AUC show no such ability. CONCLUSION: All models, including a monoexponential fit to a lower-b sub-range, achieve similar AUCs for discrimination of normal and cancer tissue. The biexponential model, which is favored statistically, also appears to provide insight into disease-related microstructural changes. Magn Reson Med 79:2346-2358, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

In vivo MR spectroscopic imaging of the prostate, from application to interpretation.

Proton magnetic resonance spectroscopic imaging (1H MRSI) enables non-invasive assessment of certain metabolites in the prostate gland. Several studies have demonstrated that this metabolic information, in combination with anatomical information from T2-weighted MR imaging significantly improves prostate cancer detection, localization and disease characterization. The technology of 1H MRSI is continuously evolving with improvements of hardware and acquisition methods. Recently, 31P and 13C MRSI of the prostate have regained new interest after a dormant period of decades. This review focuses on recent technical progress of in vivo1H MRSI of the prostate, in particular those that enhance clinical applicability at 3T with respect to commonly used techniques to examine the prostate. These developments consist of higher magnetic field strengths, and better MR coils and acquisition techniques. Besides the improvements for 1H MRSI, the developments and opportunities for 31P and 13C MRSI for the prostate are reviewed. Finally, we briefly review 13C MRS of the prostate, in particular the new possibilities with hyperpolarized substrates.

Growth inhibition in a brain metastasis model by antibody delivery using focused ultrasound-mediated blood-brain barrier disruption.

HER2-targeting antibodies (i.e. trastuzumab and pertuzumab) prolong survival in HER2-positive breast cancer patients with extracranial metastases. However, the response of brain metastases to these drugs is poor, and it is hypothesized that the blood-brain barrier (BBB) limits drug delivery to the brain. We investigated whether we could improve the response by temporary disruption of the BBB using focused ultrasound in combination with microbubbles. To study this, we inoculated 30 nude rats with HER2-positive cells derived from a brain metastasis of a breast cancer patient (MDA-MB-361). The animals were divided into three groups: a control-group that received no treatment; an antibody-only group that received six weekly treatments of trastuzumab and pertuzumab; and an ultrasound+antibody group that received trastuzumab and pertuzumab in combination with six weekly sessions of BBB disruption using focused ultrasound. In two animals, the leakiness of the tumors before disruption was evaluated using contrast-enhanced T1-weighted magnetic resonance imaging and found that the tumors were not leaky. The same technique was used to evaluate the effectiveness of BBB disruption, which was successful in all sessions. The tumor in the control animals grew exponentially with a growth constant of 0.042±0.011mm(3)/day. None of the antibody-only animals responded to the treatment and the growth constant was 0.033±0.009mm(3)/day during the treatment period. Four of the ten animals in the ultrasound+antibody-group showed a response to the treatment with an average growth constant of 0.010±0.007mm(3)/day, compared to a growth constant 0.043±0.013mm(3)/day for the six non-responders. After the treatment period, the tumors in all groups grew at similar rates. As the tumors were not leaky before BBB disruption and there were no responders in the antibody-only group, these results show that at least in some cases disruption of the BBB is necessary for a response to the antibodies in these brain metastases. Interestingly, only some of the rats responded to the treatment. We did not observe a difference in tumor volume at the start of the treatment, nor in HER2 expression or in contrast-enhancement on MRI between the responders and non-responders to explain this. Better understanding of why certain animals respond is needed and will help in translating this technique to the clinic. In conclusion, we demonstrate that BBB disruption using focused ultrasound in combination with antibody therapy can inhibit growth of breast cancer brain metastasis.

Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound.

The purpose of this study was to investigate the effects on the brain of multiple sessions of blood-brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue.

Contribution of Histopathologic Tissue Composition to Quantitative MR Spectroscopy and Diffusion-weighted Imaging of the Prostate.

PURPOSE: To determine associations of metabolite levels derived from magnetic resonance (MR) spectroscopic imaging (ie, hydrogen 1 [(1)H] MR spectroscopic imaging) and apparent diffusion coefficients (ADCs) from diffusion-weighted imaging with prostate tissue composition assessed by digital image analysis of histologic sections. MATERIALS AND METHODS: Institutional ethical review board approved this retrospective study and waived informed consent. Fifty-seven prostate cancer patients underwent an MR examination followed by prostatectomy. One hematoxylin and eosin-stained section of the resected prostate per patient was digitized and computationally segmented into nuclei, lumen, and combination of epithelial cytoplasm and stroma. On each stained section, regions of interest (ROIs) were chosen and matched to the corresponding ADC map and (1)H MR spectroscopic imaging voxels. ADC and two metabolite ratios (citrate [Cit], spermine [Spm], and creatine [Cr] to choline [Cho] and Cho to Cr plus Spm) were correlated with percentage areas of nuclei, lumen, and cytoplasm and stroma for peripheral zone (PZ), transition zone (TZ), and tumor tissue in both zones of the prostate by using a linear mixed-effect model and Spearman correlation coefficient (ρ). RESULTS: ADC and (Cit + Spm + Cr)/Cho ratio showed positive correlation with percentage area of lumen (ρ = 0.43 and 0.50, respectively) and negative correlation with percentage area of nuclei (ρ = -0.29 and -0.26, respectively). The Cho/(Cr + Spm) ratio showed negative association with percentage area of lumen (ρ = -0.40) and positive association with area of nuclei (ρ = 0.26). Percentage areas of lumen and nuclei, (Cit + Spm + Cr)/Cho ratio, and ADC were significantly different (P < .001) between benign PZ (23.7 and 7.7, 8.83, and 1.58 × 10(-3) mm(2)/sec, respectively) and tumor PZ tissue (11.4 and 12.5, 5.13, and 1.20 × 10(-3) mm(2)/sec, respectively). These parameters were also significantly different between benign TZ (20.0 and 8.2, 6.50, and 1.26 × 10(-3) mm(2)/sec, respectively) and tumor TZ tissue (9.8 and 11.2, 4.36, and 1.03 × 10(-3) mm(2)/sec, respectively). CONCLUSION: The observed correlation of (Cit + Spm + Cr)/Cho ratio and ADC of the prostate with its tissue composition indicates that components of this composition, such as percentage luminal area, contribute to the value of these MR parameters.

Computer-extracted Features Can Distinguish Noncancerous Confounding Disease from Prostatic Adenocarcinoma at Multiparametric MR Imaging.

PURPOSE: To determine the best features to discriminate prostate cancer from benign disease and its relationship to benign disease class and cancer grade. MATERIALS AND METHODS: The institutional review board approved this study and waived the need for informed consent. A retrospective cohort of 70 patients (age range, 48-70 years; median, 62 years), all of whom were scheduled to undergo radical prostatectomy and underwent preoperative 3-T multiparametric magnetic resonance (MR) imaging, including T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging, were included. The digitized prostatectomy slides were annotated for cancer and noncancerous disease and coregistered to MR imaging with an interactive deformable coregistration scheme. Computer-identified features for each of the noncancerous disease categories (eg, benign prostatic hyperplasia [BPH], prostatic intraepithelial neoplasia [PIN], inflammation, and atrophy) and prostate cancer were extracted. Feature selection was performed to identify the features with the highest discriminatory power. The performance of these five features was evaluated by using the area under the receiver operating characteristic curve (AUC). RESULTS: High-b-value diffusion-weighted images were more discriminative in distinguishing BPH from prostate cancer than apparent diffusion coefficient, which was most suitable for distinguishing PIN from prostate cancer. The focal appearance of lesions on dynamic contrast-enhanced images may help discriminate atrophy and inflammation from cancer. Which imaging features are discriminative for different benign lesions is influenced by cancer grade. The apparent diffusion coefficient appeared to be the most discriminative feature in identifying high-grade cancer. Classification results showed increased performance by taking into account specific benign types (AUC = 0.70) compared with grouping all noncancerous findings together (AUC = 0.62). CONCLUSION: The best features with which to discriminate prostate cancer from noncancerous benign disease depend on the type of benign disease and cancer grade. Use of the best features may result in better diagnostic performance.

Update on Clinical Magnetic Resonance-Guided Focused Ultrasound Applications.

In this review, several clinical applications of magnetic resonance (MR)-guided focused ultrasound (FUS) are updated. MR-guided FUS is used clinically for thermal ablation of uterine fibroids and bone metastases. Thousands of patients have successfully been treated. Transcranial MR-guided FUS has received CE certification for ablation of deep, central locations in the brain. Thermal ablation of specific parts of the thalamus can result in relief of the symptoms in a number of neurological disorders. Several approaches have been proposed for ablation of prostate and breast cancer and clinical trials should show the potential of MR-guided FUS for these and other applications.

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

OBJECTIVE: The 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 METHODS: The 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). RESULTS: In 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. CONCLUSIONS: Multiparametric 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.

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

PURPOSE: Optimization of phosphorus ((31) P) 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. METHODS: Twelve patients with prostate cancer and one healthy volunteer were scanned on a 7 T whole-body system using a (31) P endorectal coil combined with an eight-channel (1) H body array coil. T1 relaxation times were measured using progressive saturation in a two-dimensional localization sequence. (31) P MRSI was performed twice: once without NOE and once with NOE using low-power continuous wave (1) H irradiation to determine NOE enhancements. RESULTS: T1 relaxation times of (31) P metabolites in the human prostate at 7 T varied between 3.0 and 8.3 s. Positive but variable NOE enhancements were measured for most metabolites. Remarkably, the (31) P MR spectra showed two peaks in chemical shift range of inorganic phosphate. CONCLUSION: Knowledge of T1 relaxation times and NOE enhancements enables protocol optimization for (31) P MRSI of the prostate at 7 T. With a strongly reduced (31) P flip angle (≤ 45°), a (31) P MRSI dataset with optimal signal-to-noise ratio per unit time can be obtained within 15 minutes. The NOE enhancement can improve fitting accuracy, but its variability requires further investigation.

Metabolite ratios in 1H MR spectroscopic imaging of the prostate.

In (1)H MR spectroscopic imaging ((1)H-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 (1)H-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 (1)H-MRSI.

Mapping of prostate cancer by 1H MRSI.

In many studies, it has been demonstrated that (1)H 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.

In vivo (1) H MR spectroscopic imaging of aggressive prostate cancer: can we detect lactate?

PURPOSE: A semi-LASER sequence was optimized for in vivo lactate detection in the prostate. METHODS: The ethical committee waived the need for informed consent to measure 17 patients with high grade prostate cancer on a 3T system. A semi-LASER sequence was used with an echo time of 144 ms and optimized interpulse timing for a spectral citrate shape with high signal intensity. An LCModel basis set was developed for fitting choline, creatine, spermine, citrate, and lactate and was used to fit all spectra in tumor-containing voxels. For patients without detectable lactate, the minimal detectable lactate concentration was determined by adding in all spectra of tumor tissue a simulated lactate signal. The amplitude of the simulated lactate signal was iteratively decreased until its fit reached a Cramér Rao lower bound >20%, which was then set as the patient-specific detection limit. RESULTS: In none of the patients a convincing lactate signal was found. We estimated that on average the lactate levels in high grade prostate cancer are below 1.5 mM (range 0.9-3.5 mM), Interestingly, in one patient with extensive necrosis in the tumor biopsy samples (Gleason score 5+5), large lipid resonances were observed, which originated from the tumor. CONCLUSION: The minimal detectable lactate concentration of 1.5 mM in high grade prostate cancer indicates that if lactate is increased it remains at low concentrations.

Phosphorus magnetic resonance spectroscopic imaging at 7 T in patients with prostate cancer.

OBJECTIVES: The aim of this study was to identify characteristics of phosphorus (P) spectra of the human prostate and to investigate changes of individual phospholipid metabolites in prostate cancer through in vivo P magnetic resonance spectroscopic imaging (MRSI) at 7 T. MATERIALS AND METHODS: In this institutional review board-approved study, 15 patients with biopsy-proven prostate cancer underwent T2-weighted magnetic resonance imaging and 3-dimensional P 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. RESULTS: Signals of phosphoethanolamine (PE) and phosphocholine (PC) were present and well resolved in most P 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 P 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. CONCLUSIONS: Phosphorus 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 P 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.

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

PURPOSE: 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. METHODS: Nine healthy volunteers and 12 prostate cancer patients were scanned on a 7 T whole-body system. Preparation consisted of B0 and radiofrequency shimming and localized flip angle calibration. T1 and T2 relaxation times were measured and used to define the T2w-TSE protocol. T2w imaging was performed using a TSE sequence (pulse repetition time/echo time 3000-3640/71 ms) with prolonged excitation and refocusing pulses to reduce specific absorption rate. RESULTS: High quality T2w TSE imaging was performed in less than 2 min in all subjects. Tumors of patients with gold-standard tumor localization (MR-guided biopsy or prostatectomy) were well visualized on 7 T imaging (n = 3). The number of consecutive slices achievable within a 10-g averaged specific absorption rate limit of 10 W/kg was ≥28 in all subjects, sufficient for full prostate coverage with 3-mm slices in at least one direction. CONCLUSION: High quality T2w TSE prostate imaging can be performed routinely and within specific absorption rate limits at 7 T with an external transceive body array.

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 Spearman's 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.

Quality control of prostate 1 H MRSI data.

MRSI of prostate cancer provides a potential clinical tool to aid in the detection and characterisation of this disease, but its clinical use is limited by the need for the specialist training of radiologists to read these datasets. An essential part of this reading is the assessment of the usability and reliability of MRSI spectra because they can be affected by artefacts such as poor signal to noise, lipid signal contamination and broad resonances that could cause errors of interpretation. We have developed an automated quality control algorithm that classifies every voxel of an MRSI dataset as either acceptable or unacceptable for further analysis, based on the spectral profile alone. The method was trained and tested based on a gold standard of agreement of four experts. It was highly accurate: testing with a novel set of data from MRSI patients produced agreement with the experts' consensus decisions with a specificity of 0.95 and sensitivity of 0.95. This method provides fast quality control of three-dimensional MRSI datasets of the prostate, removing the need for radiologists to perform this time consuming, but necessary, task prior to further analysis.

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.

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

(31)P 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 (31)P MR spectroscopic imaging with relevant spatial resolution in a clinically acceptable measurement time. To this end, a (31)P endorectal coil was developed and combined with an eight-channel (1)H 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 (31)P endorectal coil had no influence on the specific absorption rate levels and temperature distribution of the external eight-channel (1)H 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 (1)H array coil was allowed. For transmitting with the (31)P 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 (31)P MR spectroscopic imaging produced spectra from the entire prostate in 18 min with a spatial resolution of 4 cm(3). 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.