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Background: Although the biological characteristics of uterine fibroids (UF) have implications for therapy choice and effectiveness, there is limited MRI data about these characteristics. Currently, the Funaki classification and Scaled Signal Intensity (SSI) are used to predict treatment outcome but both screening-tools appear to be suboptimal. Therefore, multiparametric and quantitative MRI was studied to evaluate various biological characteristics of UF., Methods: 87 patients with UF underwent an MRI-examination. Differences between UF tissues and myometrium were investigated using T2-mapping, Apparent Diffusion Coefficient (ADC) maps with different b-value combinations, contrast-enhanced T1-weighted and T2-weighted imaging. Additionally, the Funaki classification and SSI were calculated., Results: Significant differences between myometrium and UF tissue in T2-mapping (p = 0.001), long-TE ADC low b-values (p = 0.002), ADC all b-values (p < 0.001) and high b-values (p < 0.001) were found. Significant differences between Funaki type 3 versus type 1 and 2 were observed in SSI (p < 0.001) and T2-values (p < 0.001). Significant correlations were found between SSI and T2-mapping (p < 0.001; ρ s  = 0.82), ADC all b-values (p = 0.004; ρ s  = 0.31), ADC high b-values (p < 0.001; ρ s  = 0.44) and long-TE ADC low b-values (p = 0.004; ρ s  = 0.31)., Conclusions: Quantitative MR-data allowed us to distinguish UF tissue from myometrium and to discriminate different UF tissue types and may, therefore, be a useful tool to predict treatment outcome/determine optimal treatment modality.

Purpose. To further validate the prognostic power of the biomarker PDE4D7, we investigated the correlation of PDE4D7 scores adjusted for presurgical clinical variables with longitudinal postsurgical biological outcomes. Methods. RNA was extracted from biopsy punches of resected tumors (550 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). Cox regression and survival were applied to correlate PDE4D7 scores with patient outcomes. Logistic regression was used to combine the clinical CAPRA score with PDE4D7. Results. In univariate analysis, the PDE4D7 score was significantly associated with PSA recurrence after prostatectomy in both studied patient cohorts' analysis (HR 0.53; 95% CI 0.41-0.67; p<1.0E-04 and HR 0.47; 95% CI 0.33-0.65; p<1.0E-04, respectively). After adjustment for the presurgical clinical variables preoperative PSA, PSA density, biopsy Gleason, clinical stage, percentage tumor in the biopsy (data only available for RP cohort), and percentage of positive biopsies, the HR was 0.49 (95% CI 0.38-0.64; p<1.0E-04) and 0.43 (95% CI 0.29-0.63; p<1.0E-04), respectively. The addition of the PDE4D7 to the clinical CAPRA score increased the AUC by 5% over the CAPRA score alone (0.82 versus 0.77; p=0.004). This combination model stratified 14.6% patients of the DB cohort to no risk of biochemical relapse (NPV 100%) over a follow-up period of up to 15 years. Conclusions. The PDE4D7 score provides independent risk information for pretreatment risk stratification. Combining CAPRA with PDE4D7 scores significantly improved the clinical risk stratification before surgery.

Purpose: Increased blood-brain barrier permeability (BBBP) can result from ischemia. In this study the relation between stroke severity, patient characteristics and admission BBBP values measured with CT-perfusion (CTP) was investigated in acute ischemic stroke patients., Methods: From prospective data of the Dutch Acute Stroke Study 149 patients with a middle cerebral artery stroke and extended CTP were selected. BBBP values were measured in the penumbra and infarct core as defined by CTP thresholds, and in the contra-lateral hemisphere. The relation between stroke (severity) variables and patient characteristics, including early CT signs, dense vessel sign (DVS), time to scan and National Institute of Health Stroke Score (NIHSS), and BBBP parameters in penumbra and infarct core was quantified with regression analysis., Results: Early CT signs were related to higher BBBP values in the infarct core (B = 0.710), higher ipsi- to contra-lateral BBBP ratios (B = 0.326) and higher extraction ratios in the infarct core (B = 16.938). Females were found to have lower BBBP values in penumbra and infarct core (B = - 0.446 and - 0.776 respectively) and lower extraction ratios in the infarct core (B = - 10.463). If a DVS was present the ipsi- to contra-lateral BBBP ratios were lower (B = - 0.304). There was no relation between NIHSS or time to scan and BBBP values., Conclusion: Early CT signs are related to higher BBBP values in the infarct core, suggesting that only severe ischemic damage alters BBBP within the first hours after symptom onset.

Aim: To compare image quality of head and neck computed tomography angiography (CTA) reconstructed with filtered back projection (FBP), hybrid iterative reconstruction (HIR) and model-based iterative reconstruction (MIR) algorithms., Materials and Methods: The raw data of 34 studies were simultaneously reconstructed with FBP, HIR (iDose(4), Philips Healthcare, Best, the Netherlands), and with a prototype version of a MIR algorithm (IMR, Philips Healthcare). Objective (contrast-to-noise ratio [CNR], vascular contrast, automatic vessel analysis [AVA], stenosis grade) and subjective image quality (ranking at level of the circle of Willis, carotid bifurcation, and shoulder) of the five reconstructions were compared using repeated-measures analysis of variance (ANOVA) and post-hoc analysis., Results: Vascular contrast was significantly higher in both the circle of Willis and carotid bifurcation with both levels of MIR compared to the other reconstruction methods (all p<0.0001). The CNR was highest for high MIR, followed by low MIR, high HIR, mid HIR and FBP (p<0.001 except low MIR versus high HIR; p>0.33). AVA showed most complete carotids in both MIR-levels, followed by high HIR (p>0.08), mid HIR (p<0.023) and FBP (p<0.010), vertebral arteries completeness was similar (p=0.40 and p=0.06). Stenosis grade showed no significant differences (p=0.16). High HIR showed the best subjective image quality at the circle of Willis and carotid bifurcation level, followed by mid HIR. At shoulder level, low MIR and high HIR were ranked best, followed by high MIR., Conclusion: Objectively, MIR significantly improved the overall image quality, reduced image noise, and improved automated vessel analysis, whereas FBP showed the lowest objective image quality. Subjectively, the highest level of HIR was considered superior at the level of the circle of Willis and the carotid bifurcation, and along with the lowest level of MIR for the origins of the neck arteries at shoulder level., (Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: Perfusion imaging is increasingly used for postoperative evaluation of extracranial to intracranial (EC-IC) bypass surgery. Altered hemodynamics and delayed arrival of the contrast agent in the area fed by the bypass can influence perfusion measurement. We compared perfusion asymmetry obtained with different algorithms in EC-IC bypass surgery patients., Methods: We retrospectively identified all patients evaluated with computed tomography perfusion (CTP) between May 2007 and May 2011 after EC-IC bypass surgery at our institution. CTP images were analyzed with three perfusion algorithms that differ among their ability to anticipate for delayed arrival time of contrast material: the delay-sensitive first-moment mean transit time (fMTT), the semi-delay-sensitive standard singular value decomposition (sSVD) and the delay-insensitive block-circulant SVD (bSVD). The interhemispheric difference in bolus arrival time (ΔBAT) was determined to confirm altered hemodynamics. Interhemispheric asymmetry in perfusion values (mean transit time (MTT) difference, cerebral blood flow (CBF) ratio and cerebral blood volume (CBV) ratio) was compared between the three algorithms. Presence of a new infarct in the treated hemisphere was evaluated on follow-up imaging and perfusion asymmetry was compared between patients with and without infarction., Results: Twenty-two patients were included. The median interhemispheric difference in ΔBAT was 0.98 s. The median MTT difference was significantly smaller when calculated with the delay-insensitive algorithm than with the other algorithms (0.44 s versus 0.90 s and 0.93 s, p<0.01). The CBF ratio was similar for all algorithms (111.98 versus 112.59 and 112.60). The CBV ratio was similar for all algorithms (113.20 versus 111.95 and 113.97). There was a significant difference in MTT asymmetry between patients with and without infarction with the delay-insensitive algorithm only (1.57 s versus 0.38 s, p=0.04)., Conclusion: In patients with EC-IC bypass surgery, delay-sensitive algorithms showed larger MTT asymmetry than delay-insensitive algorithms. Furthermore, only the delay-insensitive method seems to differentiate between patients with and without infarction on follow-up., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) can be reversible or progress to cerebral infarction. In patients with a deterioration clinically diagnosed as DCI, we investigated whether CT perfusion (CTP) can distinguish between reversible ischemia and ischemia progressing to cerebral infarction., Methods: From a prospectively collected series of aSAH patients, we included those with DCI, CTP on the day of clinical deterioration, and follow-up imaging. In qualitative CTP analyses (visual assessment), we calculated positive and negative predictive value (PPV and NPV) with 95% confidence intervals (95%CI) of a perfusion deficit for infarction on follow-up imaging. In quantitative analyses, we compared perfusion values of the least perfused brain tissue between patients with and without infarction by using receiver-operator characteristic curves and calculated a threshold value with PPV and NPV for the perfusion parameter with the highest area under the curve., Results: In qualitative analyses of 33 included patients, 15 of 17 patients (88%) with and 6 of 16 patients (38%) without infarction on follow-up imaging had a perfusion deficit during clinical deterioration (p = 0.002). Presence of a perfusion deficit had a PPV of 71% (95%CI: 48-89%) and NPV of 83% (95%CI: 52-98%) for infarction on follow-up. Quantitative analyses showed that an absolute minimal cerebral blood flow (CBF) threshold of 17.7 mL/100 g/min had a PPV of 63% (95%CI: 41-81%) and a NPV of 78% (95%CI: 40-97%) for infarction., Conclusions: CTP may differ between patients with DCI who develop infarction and those who do not. For this purpose, qualitative evaluation may perform marginally better than quantitative evaluation.

Introduction: Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI., Methods: From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers., Results: Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm., Conclusion: Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose.

Many survivors of aneurysmal subarachnoid haemorrhage (aSAH) have persistent cognitive deficits. Underlying causes of these deficits have not been elucidated. We aimed to investigate if cerebral perfusion in the acute phase after aSAH measured with CT perfusion (CTP) is associated with cognitive outcome 3 months after aSAH. We included 71 patients admitted to the University Medical Center Utrecht who had CTP performed within 24 h after ictus and neuropsychological examination after 3 months. Perfusion values were measured in predefined regions of interest for cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP). The relationship with global cognitive functioning, as measured with a mean z score of all cognitive tests, was examined by linear regression analyses. Adjustments were made for age, education, method of aneurysm treatment, and presence of non-acute medical complications. TTP was associated with cognitive functioning in the univariable analysis (B = -0.042, 95 % CI -0.076 to -0.008), but not after adjustment for age (B = -0.030, 95 % CI -0.065 to 0.004). For CBF, CBV and MTT no relationship with cognitive functioning was observed. Cerebral perfusion measured with CTP within 24 h after onset of aSAH is not associated with cognitive outcome after 3 months. The lack of an association might be explained by the delay between onset of aSAH and CTP. However, CTP assessment within the first minutes after aSAH is impossible in large series of patients.

Visuospatial construction is a complex cognitive operation that is composed of a purely constructional component (visuoconstruction proper), and visuoperceptive, attentional, and decision-making components. The anatomical correlates of visuospatial construction and its cognitive subcomponents are poorly understood. The purpose of the present study was to determine the anatomical correlates of visuospatial construction by applying lesion-symptom mapping in a cohort of 111 patients with first-ever ischemic stroke. We employed the Rey-Osterrieth Complex Figure (ROCF) copy test and the Judgment of Line Orientation (JLO); both tests measure visuoperception, while only the ROCF has a constructional component. We first performed assumption-free voxel-based lesion-symptom mapping, which revealed large shared right hemispheric correlates for the ROCF and JLO in the frontal lobe, superior temporal lobe, and supramarginal gyrus. These shared anatomical correlates reflect the visuoperceptive component of the ROCF and JLO. Anatomical correlates were discordant in the right superior parietal lobule, and angular and middle occipital gyri: lesions in these regions were associated with poor performance on the ROCF, but not the JLO. Secondly, these findings were reproduced with a region of interest-based analysis that yielded a statistically significant correlation between infarct volume in the right inferior and superior parietal, angular and middle occipital cortices, and poor performance on the ROCF, but not the JLO. This discordance in anatomical correlates of the ROCF and JLO reflects the visuoconstructive component of the ROCF. These findings provide new insights in the anatomical correlates of the visuoperceptive and visuoconstructive components of the ROCF and provide evidence for a crucial role of the right inferior and superior parietal, angular and middle occipital gyri in visuoconstruction proper., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To determine the effect of computer-aided diagnosis (CAD) on less-experienced and experienced observer performance in differentiation of benign from malignant prostate lesions at 3-T multiparametric magnetic resonance (MR) imaging., Materials and Methods: The institutional review board waived the need for informed consent. Retrospectively, 34 patients were included who had prostate cancer and had undergone multiparametric MR imaging, including T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced MR imaging prior to radical prostatectomy. Six radiologists less experienced in prostate imaging and four radiologists experienced in prostate imaging were asked to characterize different regions suspicious for cancer as benign or malignant on multiparametric MR images first without and subsequently with CAD software. The effect of CAD was analyzed by using a multiple-reader, multicase, receiver operating characteristic analysis and a linear mixed-model analysis., Results: In 34 patients, 206 preannotated regions, including 67 malignant and 64 benign regions in the peripheral zone (PZ) and 19 malignant and 56 benign regions in the transition zone (TZ), were evaluated. Stand-alone CAD had an overall area under the receiver operating characteristic curve (AUC) of 0.90. For PZ and TZ lesions, the AUCs were 0.92 and 0.87, respectively. Without CAD, less-experienced observers had an overall AUC of 0.81, which significantly increased to 0.91 (P = .001) with CAD. For experienced observers, the AUC without CAD was 0.88, which increased to 0.91 (P = .17) with CAD. For PZ lesions, less-experienced observers increased their AUC from 0.86 to 0.95 (P < .001) with CAD. Experienced observers showed an increase from 0.91 to 0.93 (P = .13). For TZ lesions, less-experienced observers significantly increased their performance from 0.72 to 0.79 (P = .01) with CAD and experienced observers increased their performance from 0.81 to 0.82 (P = .42)., Conclusion: Addition of CAD significantly improved the performance of less-experienced observers in distinguishing benign from malignant lesions; when less-experienced observers used CAD, they reached similar performance as experienced observers. The stand-alone performance of CAD was similar to performance of experienced observers.

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., (© RSNA, 2012)

In this paper, a fully automatic computer-aided detection (CAD) method is proposed for the detection of prostate cancer. The CAD method consists of multiple sequential steps in order to detect locations that are suspicious for prostate cancer. In the initial stage, a voxel classification is performed using a Hessian-based blob detection algorithm at multiple scales on an apparent diffusion coefficient map. Next, a parametric multi-object segmentation method is applied and the resulting segmentation is used as a mask to restrict the candidate detection to the prostate. The remaining candidates are characterized by performing histogram analysis on multiparametric MR images. The resulting feature set is summarized into a malignancy likelihood by a supervised classifier in a two-stage classification approach. The detection performance for prostate cancer was tested on a screening population of 200 consecutive patients and evaluated using the free response operating characteristic methodology. The results show that the CAD method obtained sensitivities of 0.41, 0.65 and 0.74 at false positive (FP) levels of 1, 3 and 5 per patient, respectively. In conclusion, this study showed that it is feasible to automatically detect prostate cancer at a FP rate lower than systematic biopsy. The CAD method may assist the radiologist to detect prostate cancer locations and could potentially guide biopsy towards the most aggressive part of the tumour., (© 2012 Institute of Physics and Engineering in Medicine)

Multiparametric magnetic resonance imaging (MRI) has the potential of being the ideal prostate cancer (PCa) assessment tool. Information gathered with multiparametric MRI can serve therapy choice, guidance of interventions, and treatments. The purpose of this review is to discuss the potential role of multiparametric MRI in focal therapy with respect to patient selection and directing (robot-guided) biopsies and intensity-modulated radiation therapy (IMRT). Multiparametric MRI is a versatile and promising technique. It appears to be the best available imaging technique at the moment in localizing, staging (primary as well as recurrent disease, and local as well as distant disease), determining aggressiveness, and volume of PCa. However, larger study populations in multicenter settings have to confirm these promising results. However, before such studies can be performed more research is needed in order to achieve standardized imaging protocols., (Copyright © 2011 Wiley Periodicals, Inc.)

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., (© RSNA, 2011.)

In this study, computer-assisted analysis of prostate lesions was researched by combining information from two different magnetic resonance (MR) modalities: T2-weighted (T2-w) and dynamic contrast-enhanced (DCE) T1-w images. Two issues arise when incorporating T2-w images in a computer-aided diagnosis (CADx) system: T2-w values are position as well as sequence dependent and images can be misaligned due to patient movement during the acquisition. A method was developed that computes T2 estimates from a T2-w and proton density value and a known sequence model. A mutual information registration strategy was implemented to correct for patient movement. Global motion is modelled by an affine transformation, while local motion is described by a volume preserving non-rigid deformation based on B-splines. The additional value to the discriminating performance of a DCE T1-w-based CADx system was evaluated using bootstrapped ROC analysis. T2 estimates were successfully computed in 29 patients. T2 values were extracted and added to the CADx system from 39 malignant, 19 benign and 29 normal annotated regions. T2 values alone achieved a diagnostic accuracy of 0.85 (0.77-0.92) and showed a significantly improved discriminating performance of 0.89 (0.81-0.95), when combined with DCE T1-w features. In conclusion, the study demonstrated a simple T2 estimation method that has a diagnostic performance such that it complements a DCE T1-w-based CADx system in discriminating malignant lesions from normal and benign regions. Additionally, the T2 estimate is beneficial to visual inspection due to the removed coil profile and fixed window and level settings.

The feasibility of an automated calibration method for estimating the arterial input function when calculating pharmacokinetic parameters from Dynamic Contrast Enhanced MRI is shown. In a previous study, it was demonstrated that the computer aided diagnoses (CADx) system performs optimal when per patient calibration was used, but required manual annotation of reference tissue. In this study we propose a fully automated segmentation method that tackles this limitation and tested the method with our CADx system when discriminating prostate cancer from benign areas in the peripheral zone. A method was developed to automatically segment normal peripheral zone tissue (PZ). Context based segmentation using the Otsu histogram based threshold selection method and by Hessian based blob detection, was developed to automatically select PZ as reference tissue for the per patient calibration. In 38 consecutive patients carcinoma, benign and normal tissue were annotated on MR images by a radiologist and a researcher using whole mount step-section histopathology as standard of reference. A feature set comprising pharmacokinetic parameters was computed for each ROI and used to train a support vector machine (SVM) as classifier. In total 42 malignant, 29 benign and 37 normal regions were annotated. The diagnostic accuracy obtained for differentiating malignant from benign lesions using a conventional general patient plasma profile showed an accuracy of 0.65 (0.54-0.76). Using the automated segmentation per patient calibration method the diagnostic value improved to 0.80 (0.71-0.88), whereas the manual segmentation per patient calibration showed a diagnostic performance of 0.80 (0.70-0.90). These results show that an automated per-patient calibration is feasible, a significant better discriminating performance compared to the conventional fixed calibration was obtained and the diagnostic accuracy is similar to using manual per-patient calibration.

A novel automated computerized scheme has been developed for determining a likelihood measure of malignancy for cancer suspicious regions in the prostate based on dynamic contrast-enhanced magnetic resonance imaging (MRI) (DCE-MRI) images. Our database consisted of 34 consecutive patients with histologically proven adenocarcinoma in the peripheral zone of the prostate. Both carcinoma and non-malignant tissue were annotated in consensus on MR images by a radiologist and a researcher using whole mount step-section histopathology as standard of reference. The annotations were used as regions of interest (ROIs). A feature set comprising pharmacokinetic parameters and a T1 estimate was extracted from the ROIs to train a support vector machine as classifier. The output of the classifier was used as a measure of likelihood of malignancy. Diagnostic performance of the scheme was evaluated using the area under the ROC curve. The diagnostic accuracy obtained for differentiating prostate cancer from non-malignant disorders in the peripheral zone was 0.83 (0.75-0.92). This suggests that it is feasible to develop a computer aided diagnosis system capable of characterizing prostate cancer in the peripheral zone based on DCE-MRI.

Twelve patients with superficial bladder cancer were treated with intravesical instillations of Rubratin (ASTA Pharma AG, Frankfurt, Germany), a cell-wall preparation of Nocardia rubra. The objective was to compare the immunostimulating effect of Rubratin with that of bacillus Calmette-Guérin (BCG). Local immunostimulation was determined by cytokine induction in serially collected urine samples during the first 24 h after each instillation, leukocyte influx into the urine, and phenotypic analysis of the lymphocyte fraction. Levels of Rubratin-induced interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha were significantly elevated compared with pretherapy levels. Rubratin induced leukocyte influx into the urine. T-cell activation (IL-2 receptor and human leukocyte antigen-DR expression) can be induced, and CD4:CD8 cell ratios can be increased. All parameters indicated that Rubratin-induced immunostimulation was less than that associated with BCG. In conclusion, although local Rubratin-induced immunostimulation occurs in a limited number of patients, the amount of immunocompetent cells attracted to the bladder seems to be less than that associated with BCG therapy, thus resulting in lower levels of cytokine production (which may reflect less clinical efficacy).

Immunotherapy with intravesical instillation of bacillus Calmette-Guérin (BCG) is an effective treatment for superficial bladder carcinoma. In the present study the BCG-induced immunological reaction in the guinea pig (PPD skin test, bladder wall infiltrates and number of cells in the iliac lymph nodes) was investigated after intravesical pretreatment with pentosan polysulphate (PPS), which modulated BCG attachment to the bladder wall. Pentosan polysulfate is a molecule comparable to the naturally occurring glycosaminoglycans (GAGs) of the bladder mucosa. The data obtained after six weekly instillations of BCG-RIVM (5 x 10(6) - 5 x 10(7) cfu) with or without preinstillation with PPS (10 mg. in 1 ml. for 0.5 hour) suggested an elevation of the immunological reaction to intravesical BCG. A strong binding capacity of PPS to the mammalian bladder wall was observed. In addition, and in contrast to bacteria commonly causing cystitis, a significant binding of PPS to mycobacteria was found: 3.5, 3.6 and 3.1 micrograms./ml. dry weight of BCG Connaught, RIVM and Pasteur, compared with 0.2, 0.3, 0.7 and 0.0 microgram./mg. dry weight of Escherichia coli, Streptococcus faecalis, Klebsiella pneumoniae and Proteus. The results suggest that PPS enhances the attachment of BCG to the bladder wall, resulting in an increased BCG-induced immunological reaction in the guinea pig. It may be speculated that pretreatment with PPS may increase the efficacy of BCG therapy in man, especially in those patients not exhibiting an immunological reaction.

This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL)1 beta, IL2, IL6, and tumor necrosis factor alpha (TNF alpha) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24 h thereafter. The mean concentration of albumin in pre-therapy specimens was 112 +/- 118 (range 2-432) micrograms albumin/ml urine, approximating 14 +/- 14 micrograms/mumol creatinine (creat) (n = 15), which was comparable to the mean pre-instillation value of 16 +/- 32 micrograms/mumol creat (n = 96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (P < 0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3-6. A significant correlation between albumin and concentration of the cytokines IL1 beta, IL2, IL6, and TNF alpha was found (P < 0.01), correlation coefficients (r) being 0.56, 0.56, 0.67, and 0.71 (n = 418), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The study was initiated as an in vitro approach to the situation existing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell line T24 treated with BCG was investigated. A 24-h treatment of T24 cells with BCG resulted in a tenfold higher secretion of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) when compared with T24 cells treated with Escherichia coli, Streptococcus faecalis or a cell wall preparation of Nocardia rubra (N-CWS). No secretion of IL-1 beta and IL-2 was detected. Pre-exposing T24 cells to BCG for various periods of time indicated that a minimum exposure time of 0.5-1 h was required to upregulate IL-6 and TNF alpha production. Extending the BCG pre-exposure time to 2 and 3 h further increased the rate of cytokine production. No significant difference was found, however, between the rate of secretion initiated after a 2-h or 3-h pre-exposure period. The amounts of these cytokines secreted in the presence of BCG-conditioned medium did not differ significantly from the constitutively secreted amounts, excluding an effect of products possibly secreted by BCG on the upregulation of IL-6 and TNF alpha. In addition, upregulation of cytokine production appeared to be dependent on the concentration of BCG. The results suggest that cytokines may be produced by urothelial tumor cells after intravesical instillation in patients with superficial bladder cancer, which may play a role in the mode of action of BCG.