Comparison of two-dimensional measurement with three-dimensional volume rendering for the assessment of loss of domain in incisional hernia patients.

PURPOSE: We aimed to compare simple two-dimensional (2D) measurement with comprehensive three-dimensional (3D) volume rendering to determine loss of domain (LOD), a clinically important decision-making feature for incisional hernia repair. METHODS: In this single-center retrospective study, we analyzed the CT scans of a consecutive cohort of adult patients with a midline incisional hernia. The hernia sac- and abdominal cavity volumes were obtained by two different methods. The 2D method estimated the volumes using the corresponding height, width, and depth. The 3D method comprised of a volume rendering tool. For both methods, LOD was calculated according to the Sabbagh ratio (hernia sac volume / (hernia sac volume + abdominal cavity volume)). Taking the 3D method as the reference standard, the performance of the 2D method was expressed as positive predictive value (PPV) and negative predictive value (NPV) for LOD of more than- and less than 20%. The agreement between both methods was expressed as Cohen's kappa coefficient (kappa). RESULTS: We analyzed 92 CT scans. Agreement between both methods was high (kappa = 0.854, p = 0.0001); all 67 measurements for which the 2D method assessed LOD to be less than 20% were correctly classified (NPV = 100%), and 20 of 25 measurements for which the 2D method assessed LOD to be more than 20% were correctly classified (PPV = 80%). CONCLUSIONS: The 2D method can exclude patients from perioperative actions needed for a more complex hernia. Since this method is easy to use and less time-consuming, it seems useful for the routine radiological assessment of LOD in clinical practice.

Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC experience.

AIM: Perihilar cholangiocarcinoma (PHC) is a challenging disease and requires aggressive surgical treatment in order to achieve curation. The assessment and work-up of patients with presumed PHC is multidisciplinary, complex and requires extensive experience. The aim of this paper is to review current aspects of diagnosis, preoperative work-up and extended resection in patients with PHC from the perspective of our own institutional experience with this complex tumor. METHODS: We provided a review of applied modalities in the diagnosis and work-up of PHC according to current literature. All patients with presumed PHC in our center between 2000 and 2016 were identified and described. The types of resection, surgical techniques and outcomes were analyzed. RESULTS AND CONCLUSION: Upcoming diagnostic modalities such as Spyglass and combinations of serum biomarkers and molecular markers have potential to decrease the rate of misdiagnosis of benign, inflammatory disease. Assessment of liver function with hepatobiliary scintigraphy provides better information on the future remnant liver (FRL) than volume alone. The selective use of staging laparoscopy is advisable to avoid futile laparotomies. In patients requiring extended resection, selective preoperative biliary drainage is mandatory in cholangitis and when FRL is small (< 50%). Preoperative portal vein embolization (PVE) is used when FRL volume is less than 40% and optionally includes the left portal vein branches to segment 4. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as alternative to PVE is not recommended in PHC. N2 positive lymph nodes preclude long-term survival. The benefit of unconditional en bloc resection of the portal vein bifurcation is uncertain. Along these lines, an aggressive surgical approach encompassing extended liver resection including segment 1, regional lymphadenectomy and conditional portal venous resection translates into favorable long-term survival.

The prostate cancer detection rates of CEUS-targeted versus MRI-targeted versus systematic TRUS-guided biopsies in biopsy-naïve men: a prospective, comparative clinical trial using the same patients.

BACKGROUND: The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10-12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these "blind" systematic biopsies with reliable imaging-based targeted biopsies. METHODS/DESIGN: In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols. DISCUSSION: This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantification. TRIAL REGISTRATION: The Dutch Central Committee on Research Involving Human Subjects registration number NL52851.018.15, registered on 3 Nov 2015. Clinicaltrials.gov database registration number NCT02831920 , retrospectively registered on 5 July 2016.

MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy.

OBJECTIVES: Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. METHODS: A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H&E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. RESULTS: Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. CONCLUSIONS: mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. KEY POINTS: • mpMRI and contrast-enhanced ultrasound are appropriate imaging modalities for assessing IRE effects • mpMRI and CEUS are the most feasible imaging modalities to visualize IRE ablation zone • The imaging is concordant with results of histopathological examination after IRE • Grey-scale US is insufficient for assessing IRE ablations.

The safety and efficacy of irreversible electroporation for the ablation of prostate cancer: a multicentre prospective human in vivo pilot study protocol.

INTRODUCTION: Current surgical and ablative treatment options for prostate cancer have a relatively high incidence of side effects, which may diminish the quality of life. The side effects are a consequence of procedure-related damage of the blood vessels, bowel, urethra or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective in destroying tumour cells and harbours the advantage of sparing surrounding tissue and vital structures. The aim of the study is to evaluate the safety and efficacy and to acquire data on patient experience of minimally invasive, transperineally image-guided IRE for the focal ablation of prostate cancer. METHODS AND ANALYSIS: In this multicentre pilot study, 16 patients with prostate cancer who are scheduled for a radical prostatectomy will undergo an IRE procedure, approximately 30 days prior to the radical prostatectomy. Data as adverse events, side effects, functional outcomes, pain and quality of life will be collected and patients will be controlled at 1 and 2 weeks post-IRE, 1 day preprostatectomy and postprostatectomy. Prior to the IRE procedure and the radical prostatectomy, all patients will undergo a multiparametric MRI and contrast-enhanced ultrasound of the prostate. The efficacy of ablation will be determined by whole mount histopathological examination, which will be correlated with the imaging of the ablation zone. ETHICS AND DISSEMINATION: The protocol is approved by the ethics committee at the coordinating centre (Academic Medical Center (AMC) Amsterdam) and by the local Institutional Review Board at the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. CONCLUSIONS: This pilot study will determine the safety and efficacy of IRE in the prostate. It will show the radiological and histopathological effects of IRE ablations and it will provide data to construct an accurate treatment planning tool for IRE in prostate tissue. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov database: NCT01790451.

Prostate cancer localization by novel magnetic resonance dispersion imaging.

Diagnosis and focal treatment of prostate cancer, the most prevalent form of cancer in men, is hampered by the limits of current clinical imaging. Angiogenesis imaging is a promising option for detection and localization of prostate cancer. It can be imaged by dynamic contrast-enhanced (DCE) MRI, assessing microvascular permeability as an indicator for angiogenesis. However, information on microvascular architecture changes associated with angiogenesis is not available. This paper presents a new model enabling the combined assessment of microvascular permeability and architecture. After the intravenous injection of a gadolinium-chelate bolus, time-concentration curves (TCCs) are measured by DCE-MRI at each voxel. According to the convective dispersion equation, the microvascular architecture is reflected in the dispersion coefficient. A solution of this equation is therefore proposed to represent the intravascular blood plasma compartment in the Tofts model. Fitting the resulting model to TCCs measured at each voxel leads to the simultaneous generation of a dispersion and a permeability map. Measurement of an arterial input function is no longer required. Preliminary validation was performed by spatial comparison with the histological results in seven patients referred for radical prostatectomy. Cancer localization by the obtained dispersion maps provided an area under the receiver operating characteristic curve equal to 0.91. None of the standard DCE-MRI parametric maps could outperform this result, motivating towards an extended validation of the method, also aimed at investigating other forms of cancer with pronounced angiogenic development.

Radiological staging in patients with hilar cholangiocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: To obtain diagnostic performance values of CT, MRI, ultrasound and 18-fludeoxyglucose positron emission tomography (PET)/CT for staging of hilar cholangiocarcinoma. METHODS: A comprehensive systematic search was performed for articles published up to March 2011 that fulfilled the inclusion criteria. Study quality was assessed with the quality assessment of diagnostic accuracy studies tool. RESULTS: 16 articles (448 patients) were included that evaluated CT (n=11), MRI (n=3), ultrasound (n=3), or PET/CT (n=1). Overall, their quality was moderate. The accuracy estimates for evaluation of CT for ductal extent of the tumour was 86%. The sensitivity and specificity estimates of CT were 89% and 92% for evaluation of portal vein involvement, 83% and 93% for hepatic artery involvement, and 61% and 88% for lymph node involvement, respectively. Data were too limited for adequate comparisons of the different techniques. CONCLUSION: Diagnostic accuracy studies of CT, MRI, ultrasound or PET/CT for staging of hilar cholangiocarcinoma are sparse and have moderate methodological quality. Data primarily concern CT, which has an acceptable accuracy for assessment of ductal extent, portal vein and hepatic artery involvement, but low sensitivity for nodal status.

Patient selection for magnetic resonance imaging of prostate cancer.

BACKGROUND: Routine magnetic resonance (MR) imaging for local staging of prostate cancer is controversial, due to moderate staging performance. However, MR imaging may be beneficial in a subgroup of patients with clinically localized prostate cancer. OBJECTIVE: To define the patient group in which local staging of prostate cancer using MR imaging is useful for treatment outcome. METHODS: We used a decision analytic model based on data found in the literature to define the patient subgroup which may benefit from local staging with MR imaging. We applied the threshold approach to calculate the threshold where direct surgery and surgery after MR imaging (surgery-MR imaging threshold) result in equal utility. Additionally, we calculated the threshold where direct radiation and radiation after MR imaging (MR imaging-radiotherapy threshold) result in equal utility. RESULTS: We found that the surgery-MR imaging threshold was at a probability of 45% of having stage > or =T(3) disease. The MR imaging-radiotherapy threshold was at a prior probability of 81% of having stage > or =T(3) disease. CONCLUSIONS: The application of the threshold approach indicated that MR imaging should be limited to patients with an intermediate-high risk of having stage T(3) disease.

Bismuth overdosing-induced reversible nephropathy in rats.

Overdosing of colloidal bismuth subcitrate (CBS), used to treat peptic ulcers and Helicobacter pylori infections, has been reported to result in serious, though reversible, nephrotoxicity in humans. However, little is known about the nature of the renal damage induced by bismuth (Bi), and no well-described experimental model exists. Single large oral CBS doses (0.75, 1.5, and 3.0 mmol Bi/kg) were administered to three groups of 20 female Wistar rats. A control group (n = 20) received only the vehicle. Standard kidney function parameters, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and the Bi content were monitored in blood, urine, liver, and kidneys for 14 days. A dose of 3.0 mmol Bi/kg, 100 times the daily therapeutic dose, caused kidney damage within 6 h as detected by proteinuria, glucosuria, and elevated plasma urea and plasma creatinine levels. The kidneys of all animals, except two that died, recovered functionally within 10 days. At a dose of 1.5 mmol Bi/kg, clinical parameters changed less and normalized within 48 h, whereas a dose of 0.75 mmol Bi/kg induced no changes. Histological evaluation revealed that the S3 tubular segment necrotized first with additional necrotization of the S1/S2 segment when more Bi was absorbed. The lesions were accompanied by interstitial infiltrates of CD45+ leukocytes. In summary, we developed a rat model for Bi-induced reversible nephropathy. A large single oral overdose of CBS administered to Wistar rats led to damage to the proximal tubule, especially in the last segment.

Accurate estimation of pharmacokinetic contrast-enhanced dynamic MRI parameters of the prostate.

Quantitative analysis of contrast-enhanced dynamic MR images has potential for diagnosing prostate cancer. Contemporary fast acquisition techniques can give sufficiently high temporal resolution to sample the fast dynamics observed in the prostate. Data reduction for parametric visualization requires automatic curve fitting to a pharmacokinetic model, which to date has been performed using least-squares error minimization methods. We observed that these methods often produce unexpectedly noisy estimates, especially for the typically fast, intermediate parameters time-to-peak and start-of-enhancement, resulting in inaccurate pharmacokinetic parameter estimates. We developed a new curve fit method that focuses on the most probable slope. A set of 10 patients annotated using histopathology was used to compare the conventional and new methods. The results show that our new method is significantly more accurate, especially in the relatively less-enhancing peripheral zone. We conclude that estimation accuracy depends on the curve fit method, which is especially important when evaluating the peripheral zone of the prostate.

MR imaging of the male pelvis.

Prostate and urinary bladder cancer are the most frequently encountered malignancies of the urinary tract. Appropriate use of the different imaging techniques is crucial for accurate assessment of prognosis and for the development of appropriate treatment planning. Especially determination of local tumor extension and detection of nodal or bone metastases is extremely important. In this regard MR imaging is the most promising imaging technique. Therefore, in this review its role in staging these malignancies is evaluated and compared with clinical staging, and other imaging techniques. Finally, future developments, such as new sequences, new contrast agents, the role of surface coils and MR-guided biopsy, are considered. Also, the preferred radiological approach is discussed.

Quantitative analysis of ultrasonic B-mode images.

Various sources of variability, such as speckle noise, depth dependence and inhomogeneous intervening tissue, are involved in B-mode images, even when using the same ultrasonic equipment with fixed settings. The behavior of these sources of variability was investigated by texture analysis of images obtained from simulations and from a tissue-mimicking phantom, a normal adult liver and a pediatric renal (Wilms') tumor. First-order statistics (MEAN and SNR) and second-order statistics from the co-occurrence matrix (ENT and COR) were calculated. In a phantom, the SNR and ENT show a clear depth dependence. In biological tissue, the variability is mainly caused by the speckle noise and inhomogeneous intervening tissue. In addition, almost the entire range of the COR feature is present in images of liver and tumor. Furthermore, all the features calculated in windows of 1 cm2 exhibit an overlap among the different media. With the second-order features, it is possible to discriminate 85% reliable (average) between the normal, adult, liver and the pediatric renal tumor above a window size of 9 cm2. The SNR can not discriminate between these tissues. The maximum resolution of 9 cm2 reveals a serious limitation of parametric imaging. Finally, the features reproduce well in the case of follow-up of an abdominal tumor during chemotherapy.

Contrast-enhanced 3D-TOF MRA of peripheral vessels: intravascular versus extracellular MR contrast media.

MR contrast media have been used to improve MR angiography (MRA). Their effect has been particularly beneficial for extracranial MRA. This study evaluated the efficacy of a new formulation of ultrasmall superparamagnetic iron oxide particles (USPIO) on three-dimensional (3D) time of flight (TOF) MRA in the pelvis and lower limb circulation. Each of six dogs received 3 mg/kg of USPIO and .2 mmol/kg of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) bis-methylamide (BMA) by intravenous infusion on separate examinations. Precontrast and postcontrast 3D-TOF MRA images of the lower extremities were acquired over the course of 45 minutes postinjection. Signal intensity (SI) was measured on axial views along the external iliac, femoral, and popliteal arteries. USPIO provided clear demarcation of the major primary, secondary, and tertiary vessels and the improved contrast-to-noise ratio (CNR) was maintained for 45 minutes. Gd-DTPA-BMA provided less signal enhancement than USPIO. The increase in CNR with this agent had significantly declined by 15 minutes after injection. The major vessels could no longer be visualized at 30 and 45 minutes after injection of Gd-DTPA-BMA This study demonstrates the efficacy of USPIO as a contrast medium for 3D-TOF MRA. It was concluded that USPIO provided effective and persistent enhancement of the peripheral vessels.

Follow-up of Wilms' tumour during pre-operative chemotherapy by qualitative and quantitative sonography.

OBJECTIVES: Evaluation of textural changes in Wilms' tumour during chemotherapy by qualitative and quantitative ultrasonography. METHODS: Sonograms of Wilms' tumours during chemotherapy were retrospectively evaluated (N=33) and compared with histopathology. Textural changes were prospectively quantified (N=6) by mean echogenicity (MEAN) and coefficient of variation (CV) of grey levels. RESULTS: Interobserver agreement for volume measurements was strong and for follow-up of sonolucencies moderate. Chemotherapy caused significant volume reduction and two major patterns of change in sonolucencies were observed; either increase or no change. No relationship between sonolucencies and volume changes was present. Sonolucencies yielded an underestimation of necrosis (P<0.001). Trends in MEAN and CV differed between patients. CONCLUSIONS: Volume was the most objective sonographic tumour response parameter. Changes in sonolucencies may provide additional information on tumour response. However, sonolucencies are not an accurate measure of total tumour necrosis. It was not possible to differentiate Wilms' tumour chemotherapy responders from non-responders by MEAN and CV.