Arnoud W. Postema

Dynamic contrast-enhanced ultrasound parametric imaging for the detection of prostate cancer

To investigate the value of dynamic contrast‐enhanced (DCE)‐ultrasonography (US) and software‐generated parametric maps in predicting biopsy outcome and their potential to reduce the amount of negative biopsy cores.

Histopathological Outcomes after Irreversible Electroporation for Prostate Cancer: Results of an Ablate and Resect Study

PURPOSE Irreversible electroporation is a tissue ablation modality that uses high voltage electric energy to induce an increase in cell membrane permeability. This causes destabilization of the existing cellular transmembrane potential leading to cell death, due to the inability to maintain cellular homeostasis. This phase I-II study was designed to evaluate the histopathological outcomes of irreversible electroporation to prostate and surrounding tissue in radical prostatectomy specimens. MATERIALS AND METHODS Sixteen patients with prostate cancer underwent an irreversible electroporation ablation without curative intent, followed by radical prostatectomy scheduled 4 weeks later. For histopathological examination of the prostate, whole mounted tissue slices were examined by dedicated genitourinary pathologists. The borders of the ablation zone and residual tumor were outlined on the slides. RESULTS The irreversible electroporation ablation zones were characterized as areas of fibrosis, necrosis and loss of epithelial tissue in terms of denudation in the glandular structures. The ablation zone was well demarcated, showing trenchant delineations between viable and nonviable tissue. The ablated tissue showed mild to moderate inflammation, with atrophic cells in 1 case. The area was surrounded by hemorrhage at the location of the electrodes. No skip lesions or viable tissue was seen in the ablation zone. Fibrinoid necrosis of the neurovascular bundle was observed in 13 patients and denudation of the urothelium of the prostatic urethra was seen in 9. CONCLUSIONS Histopathological assessment of the prostate 4 weeks after irreversible electroporation ablation showed sharply demarcated fibrotic and necrotic tissue in the ablation zone. No viable tissue was observed in the irreversible electroporation ablation zone.

Ultrasound-contrast-agent dispersion and velocity imaging for prostate cancer localization

&NA; Prostate cancer (PCa) is the second‐leading cause of cancer death in men; however, reliable tools for detection and localization are still lacking. Dynamic Contrast Enhanced UltraSound (DCE‐US) is a diagnostic tool that is suitable for analysis of vascularization, by imaging an intravenously injected microbubble bolus. The localization of angiogenic vascularization associated with the development of tumors is of particular interest. Recently, methods for the analysis of the bolus convective dispersion process have shown promise to localize angiogenesis. However, independent estimation of dispersion was not possible due to the ambiguity between convection and dispersion. Therefore, in this study we propose a new method that considers the vascular network as a dynamic linear system, whose impulse response can be locally identified. To this end, model‐based parameter estimation is employed, that permits extraction of the apparent dispersion coefficient (D), velocity (v), and Péclet number (Pe) of the system. Clinical evaluation using data recorded from 25 patients shows that the proposed method can be applied effectively to DCE‐US, and is able to locally characterize the hemodynamics, yielding promising results (receiver‐operating‐characteristic curve area of 0.84) for prostate cancer localization. HighlightsA novel contrast‐ultrasound method is proposed for prostate cancer localization.Independent estimation of dispersion and velocity of ultrasound contrast agents.Tumors show increased velocity estimates, and reduced dispersion estimates.Clinical evaluation on 25 patients yields promising results (ROC area 0.84). Graphical abstract Figure. No caption available.

Ultrasound modalities and quantification: developments of multiparametric ultrasonography, a new modality to detect, localize and target prostatic tumors.

Purpose of review An imaging tool providing reliable prostate cancer (PCa) detection and localization is necessary to improve the diagnostic pathway with imaging targeted biopsies. This review presents the latest developments in existing and novel ultrasound modalities for the detection and localization of PCa. Recent findings The ultrasound modalities that were very promising on introduction (HistoScanning and Doppler) have shown a wane in performance when tested in larger patient populations. In the meantime, novel ultrasound modalities have emerged in the field of PCa detection. Modalities, such as shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) show very promising results. SWE produces an absolute elasticity measure and removes the need for manual compression of the tissue. The former allows comparison between scans and patients, the latter reduces the interoperator variability. Quantification of CEUS enables easily interpretable and accurate imaging of the microvascular changes associated with clinically significant prostate tumors. Summary The novel ultrasound modalities of SWE and CEUS imaging open the door for taking targeted biopsies based on the detection and localization of PCa by these novel modalities. This potentially improves PCa detection wherein significantly reducing the number of biopsy cores.

3D surface-based registration of ultrasound and histology in prostate cancer imaging

Several transrectal ultrasound (TRUS)-based techniques aiming at accurate localization of prostate cancer are emerging to improve diagnostics or to assist with focal therapy. However, precise validation prior to introduction into clinical practice is required. Histopathology after radical prostatectomy provides an excellent ground truth, but needs accurate registration with imaging. In this work, a 3D, surface-based, elastic registration method was developed to fuse TRUS images with histopathologic results. To maximize the applicability in clinical practice, no auxiliary sensors or dedicated hardware were used for the registration. The mean registration errors, measured in vitro and in vivo, were 1.5±0.2 and 2.1±0.5mm, respectively.

Contrast-ultrasound dispersion imaging of cancer neovascularization by mutual-information analysis

Being an established marker for cancer growth, neovascularization is probed by several approaches with the aim of cancer imaging. Recently, analysis of the dispersion kinetics of ultrasound contrast agents (UCAs) has been proposed as a promising approach for localizing neovascularization in prostate cancer. Determined by multipath trajectories through the microvasculature, dispersion enables characterization of the microvascular architecture and, therefore, localization of cancer neovascularization. Analysis of the spatiotemporal similarity among indicator dilution curves (IDCs) measured at each pixel by dynamic contrast-enhanced ultrasound imaging has been proposed to assess the local dispersion kinetics of UCAs. Only linear similarity measures, such as temporal correlation or spectral coherence, have been used up until now. Here we investigate the use of nonlinear similarity measures by estimation of the statistical dependency between IDCs. In particular, dispersion maps are generated by estimation of the mutual information between IDCs. The method is tested for prostate cancer localization and the results compared with the histology results in 15 patients referred for radical prostatectomy because of biopsy-proven prostate cancer. With sensitivity and specificity equal to 84% and 85%, respectively, and receiver operating characteristic curve area equal to 0.92, our results outperformed those obtained by any other parameter, motivating further validation with a larger dataset and with other types of cancer.

Entropy of Ultrasound-Contrast-Agent Velocity Fields for Angiogenesis Imaging in Prostate Cancer

Prostate cancer care can benefit from accurate and cost-efficient imaging modalities that are able to reveal prognostic indicators for cancer. Angiogenesis is known to play a central role in the growth of tumors towards a metastatic or a lethal phenotype. With the aim of localizing angiogenic activity in a non-invasive manner, Dynamic Contrast Enhanced Ultrasound (DCE-US) has been widely used. Usually, the passage of ultrasound contrast agents thought the organ of interest is analyzed for the assessment of tissue perfusion. However, the heterogeneous nature of blood flow in angiogenic vasculature hampers the diagnostic effectiveness of perfusion parameters. In this regard, quantification of the heterogeneity of flow may provide a relevant additional feature for localizing angiogenesis. Statistics based on flow magnitude as well as its orientation can be exploited for this purpose. In this paper, we estimate the microbubble velocity fields from a standard bolus injection and provide a first statistical characterization by performing a spatial entropy analysis. By testing the method on 24 patients with biopsy-proven prostate cancer, we show that the proposed method can be applied effectively to clinically acquired DCE-US data. The method permits estimation of the in-plane flow vector fields and their local intricacy, and yields promising results (receiver-operating-characteristic curve area of 0.85) for the detection of prostate cancer.

Transabdominal Contrast-Enhanced Ultrasound Imaging of the Prostate

Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time-intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r(2) = 0.91 (r(2) > 0.75 for 78.6% of all prostate pixels) compared with r(2) = 0.91 (r(2) > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring.

Irreversible electroporation for the treatment of localized prostate cancer: a summary of imaging findings and treatment feedback

PURPOSE Imaging plays a crucial role in ablative therapies for prostate cancer (PCa). Irreversible electroporation (IRE) is a new treatment modality used for focal treatment of PCa. We aimed to demonstrate what imaging modalities can be used by descriptively reporting contrast-enhanced ultrasonography (CEUS), multiparametric magnetic resonance imaging (mpMRI), and grey-scale transrectal ultrasound (TRUS) results. Furthermore, we aimed to correlate quantitatively the ablation zone seen on mpMRI and CEUS with treatment planning to provide therapy feedback. METHODS Imaging data was obtained from two prospective multicenter trials on IRE for localized low- to intermediate-risk PCa. The ablation zone volume (AZV) seen on mpMRI and CEUS was 3D reconstructed to correlate with the planned AZV. RESULTS Descriptive examples are provided using mpMRI, TRUS, and CEUS for treatment planning and follow-up after IRE. The mean AZV on T2-weighted imaging 4 weeks following IRE was 12.9 cm3 (standard deviation [SD]=7.0), 5.3 times larger than the planned AZV. Linear regression showed a positive correlation (r=0.76, P = 0.002). For CEUS the mean AZV was 20.7 cm3 (SD=8.7), 8.5 times larger than the planned AZV with a strong positive correlation (r=0.93, P = 0.001). Prostate volume is reduced over time (mean= -27.5%, SD=11.9%) due to ablation zone fibrosis and deformation, illustrated by 3D reconstruction. CONCLUSION The role of imaging in conjunction with IRE is of crucial importance to guide clinicians throughout the treatment protocol. CEUS and mpMRI may provide essential treatment feedback by visualizing the ablation zone dimensions and volume.

Imaging of the dispersion coefficient of Ultrasound contrast agents by Wiener system identification for prostate cancer localization

Prostate cancer (PCa) is the most prevalent form of cancer in Western men; however, reliable tools for PCa detection and localization are lacking. Dynamic Contrast Enhanced Ultrasound (DCE-US) is a diagnostic tool that allows analysis of vascularization, by imaging an intravenously injected microbubble bolus. The localization of angiogenic vascularization associated with the development of tumors is of particular interest. Recently, methods aiming at estimating contrast dispersion to localize angiogenesis have shown promise. However, independent estimation of dispersion was not possible due to the ambiguity between dispersive and convective processes. Therefore, in this study we propose a new method that considers the vascular network as a dynamic linear system, whose impulse response can be locally identified by solving the Wiener-Hopf equations. To facilitate characterization, model-based parameter estimation is employed, permitting the determination of the apparent dispersion coefficient (D), velocity (v), and Péclet number (Pe) of the system. A preliminary clinical evaluation using data recorded from 10 patients shows that the proposed method can be applied effectively to DCE-US, and is able to locally characterize the hemodynamics in the prostate.