This review presents the current state of the art regarding multiparametric magnetic resonance (MR) imaging of prostate cancer. Technical requirements and clinical indications for the use of ...multiparametric MR imaging in detection, localization, characterization, staging, biopsy guidance, and active surveillance of prostate cancer are discussed. Although reported accuracies of the separate and combined multiparametric MR imaging techniques vary for diverse clinical prostate cancer indications, multiparametric MR imaging of the prostate has shown promising results and may be of additional value in prostate cancer localization and local staging. Consensus on which technical approaches (field strengths, sequences, use of an endorectal coil) and combination of multiparametric MR imaging techniques should be used for specific clinical indications remains a challenge. Because guidelines are currently lacking, suggestions for a general minimal protocol for multiparametric MR imaging of the prostate based on the literature and the authors' experience are presented. Computer programs that allow evaluation of the various components of a multiparametric MR imaging examination in one view should be developed. In this way, an integrated interpretation of anatomic and functional MR imaging techniques in a multiparametric MR imaging examination is possible. Education and experience of specialist radiologists are essential for correct interpretation of multiparametric prostate MR imaging findings. Supportive techniques, such as computer-aided diagnosis are needed to obtain a fast, cost-effective, easy, and more reproducible prostate cancer diagnosis out of more and more complex multiparametric MR imaging data.
Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR ...scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good‐quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi‐adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.
Abstract 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 ( Ktrans ) ( 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, Ktrans , 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 ( Ktrans 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, Ktrans , and Kep offer the best possibility to discriminate low-grade from intermediate-grade plus high-grade PCa.
Parkinson's disease is characterized by bradykinesia, rigidity, and tremor. These symptoms have been related to an increased gamma‐aminobutyric acid (GABA)ergic inhibitory drive from globus pallidus ...onto the thalamus. However, in vivo empirical evidence for the role of GABA in Parkinson's disease is limited. Some discrepancies in the literature may be explained by the presence or absence of tremor. Specifically, recent functional magnetic resonance imaging (fMRI) findings suggest that Parkinson's tremor is associated with reduced, dopamine‐dependent thalamic inhibition. Here, we tested the hypothesis that GABA in the thalamocortical motor circuit is increased in Parkinson's disease, and we explored differences between clinical phenotypes. We included 60 Parkinson patients with dopamine‐resistant tremor (n = 17), dopamine‐responsive tremor (n = 23), or no tremor (n = 20), and healthy controls (n = 22). Using magnetic resonance spectroscopy, we measured GABA‐to‐total‐creatine ratio in motor cortex, thalamus, and a control region (visual cortex) on two separate days (ON and OFF dopaminergic medication). GABA levels were unaltered by Parkinson's disease, clinical phenotype, or medication. However, motor cortex GABA levels were inversely correlated with disease severity, particularly rigidity and tremor, both ON and OFF medication. We conclude that cortical GABA plays a beneficial rather than a detrimental role in Parkinson's disease, and that GABA depletion may contribute to increased motor symptom expression.
To prospectively determine the accuracies of T2-weighted magnetic resonance (MR) imaging, dynamic contrast material-enhanced MR imaging, and quantitative three-dimensional (3D) proton MR ...spectroscopic imaging of the entire prostate for prostate cancer localization, with whole-mount histopathologic section findings as the reference standard.
This study was approved by the institutional review board, and informed consent was obtained from all patients. Thirty-four consecutive men with a mean age of 60 years and a mean prostate-specific antigen level of 8 ng/mL were examined. The median biopsy Gleason score was 6. T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and 3D MR spectroscopic imaging were performed, and on the basis of the image data, two readers with different levels of experience recorded the location of the suspicious peripheral zone and central gland tumor nodules on each of 14 standardized regions of interest (ROIs) in the prostate. The degree of diagnostic confidence for each ROI was recorded on a five-point scale. Localization accuracy and ROI-based receiver operating characteristic (ROC) curves were calculated.
For both readers, areas under the ROC curve for T2-weighted MR, dynamic contrast-enhanced MR, and 3D MR spectroscopic imaging were 0.68, 0.91, and 0.80, respectively. Reader accuracy in tumor localization with dynamic contrast-enhanced imaging was significantly better than that with quantitative spectroscopic imaging (P < .01). Reader accuracy in tumor localization with both dynamic contrast-enhanced imaging and spectroscopic imaging was significantly better than that with T2-weighted imaging (P < .01).
Compared with use of T2-weighted MR imaging, use of dynamic contrast-enhanced MR imaging and 3D MR spectroscopic imaging facilitated significantly improved accuracy in prostate cancer localization.
Objective The definition of an in vivo nodal anatomical baseline is crucial for validation of representative lymph node dissections and accompanying pathology reports of pelvic cancers, as well as ...for assessing a potential therapeutic effect of extended lymph node dissections. Therefore the number, size and distribution of lymph nodes in the pelvis were assessed with high-resolution, large field-of-view, 7 Tesla (T) magnetic resonance imaging (MRI) with frequency-selective excitation. Materials and methods We used 7 T MRI for homogeneous pelvic imaging in 11 young healthy volunteers. Frequency-selective imaging of water and lipids was performed to detect nodal structures in the pelvis. Number and size of detected nodes was measured and size distribution per region was assessed. An average volunteer-normalized nodal size distribution was determined. Results In total, 564 lymph nodes were detected in six pelvic regions. Mean number was 51.3 with a wide range of 19-91 lymph nodes per volunteer. Mean diameter was 2.3 mm with a range of 1 to 7 mm. 69% Was 2 mm or smaller. The overall size distribution was very similar to the average volunteer-normalized nodal size distribution. Conclusions The amount of in vivo visible lymph nodes varies largely between subjects, whereas the normalized size distribution of nodes does not. The presence of many small lymph nodes (less than or equal to2mm) renders representative or complete removal of pelvic lymph nodes to be very difficult. 7T MRI may shift the in vivo detection limits of lymph node metastases in the future.
The success of cellular therapies will depend in part on accurate delivery of cells to target organs. In dendritic cell therapy, in particular, delivery and subsequent migration of cells to regional ...lymph nodes is essential for effective stimulation of the immune system. We show here that in vivo magnetic resonance tracking of magnetically labeled cells is feasible in humans for detecting very low numbers of dendritic cells in conjunction with detailed anatomical information. Autologous dendritic cells were labeled with a clinical superparamagnetic iron oxide formulation or (111)In-oxine and were co-injected intranodally in melanoma patients under ultrasound guidance. In contrast to scintigraphic imaging, magnetic resonance imaging (MRI) allowed assessment of the accuracy of dendritic cell delivery and of inter- and intra-nodal cell migration patterns. MRI cell tracking using iron oxides appears clinically safe and well suited to monitor cellular therapy in humans.
In the past 15 years, encouraging clinical results for the detection of small lymph node metastases was obtained by the use of Combidex‐enhanced MRI (CEM, also known as magnetic resonance ...lymphography). Withdrawal of the European Medicines Agency approval application by the manufacturer made it impossible for patients to benefit from this agent; a loss, especially for men with prostate cancer. Current conventional imaging techniques are not as accurate as CEM is, thus a surgical diagnostic exploration (extended lymph node dissection) is still the preferred technique to evaluate the lymph nodes, resulting in peri‐ and postoperative complications. In 2013, the Radboud University Medical Center (Radboudumc) obtained all licenses and documentation for the production process of Combidex (ferumoxtran‐10), and manufactured the contrast agent under supervision of the Department of Pharmacy. Since 2014, 310 men with prostate cancer have been examined with CEM in the Radboudumc. Within this cohort, seven minor possibly contrast‐related adverse effects were observed after administration of Combidex. As the contrast agent is now back again in the Netherlands, this review highlights the working mechanism, previous results, observed side effects since the reintroduction, and the future perspectives for Combidex. WIREs Nanomed Nanobiotechnol 2018, 10:e1471. doi: 10.1002/wnan.1471
This article is categorized under:
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Combidex‐enhanced magnetic resonance imaging (MRI) at 3 T of a 53‐year‐old patient with recurrent prostate cancer after radical prostatectomy and radiotherapy (PSA‐level 3.9 ng/mL). Twenty‐seven hours after administration of Combidex benign lymph nodes have accumulated the contrast agent, becoming black on a three‐dimensional (3D) iron‐sensitive MRI scan. Metastatic lymph nodes retain signal and therefore stay white. A large (7 mm) metastatic lymph node is visible on Combidex‐enhanced MRI as a white spherical structure in two orthogonal planes through the node blue circles in coronal (a) and axial images (b). A smaller metastatic white node (2–3 mm) is indicated with red circles in the coronal (c) and axial (d) reconstructions (orthogonal planes through the node of interest) of the 3D data set. The other small spherical structures are blood vessels, best appreciated when scrolling through the 3D image data set.
A large body of published work shows that proton (hydrogen 1 (1)H) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors ...present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.
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.
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.
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.
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.
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