Andreas Wibmer

Automatic classification of prostate cancer Gleason scores from multiparametric magnetic resonance images.

Significance Gleason scores and ultimately the aggressiveness of prostate cancers determined using transrectal ultrasound (TRUS)-guided biopsy procedures could result in incorrect diagnosis in addition to patient discomfort. The Gleason scores determined from TRUS-guided biopsies often differ from immediate repeat biopsies and the biopsies determined following whole excision of the prostate. Our approach presents a highly accurate and automated method for differentiating between the high ≥7 and low Gleason score 6(3+3), as well as between 7(3+4) and 7(4+3) Gleason score cancers through multiparametric MRI combined with texture features computed on the same images. Noninvasive and accurate techniques such as ours can benefit patient care without subjecting them to unnecessary interventions. Noninvasive, radiological image-based detection and stratification of Gleason patterns can impact clinical outcomes, treatment selection, and the determination of disease status at diagnosis without subjecting patients to surgical biopsies. We present machine learning-based automatic classification of prostate cancer aggressiveness by combining apparent diffusion coefficient (ADC) and T2-weighted (T2-w) MRI-based texture features. Our approach achieved reasonably accurate classification of Gleason scores (GS) 6(3+3) vs. ≥7 and 7(3+4) vs. 7(4+3) despite the presence of highly unbalanced samples by using two different sample augmentation techniques followed by feature selection-based classification. Our method distinguished between GS 6(3+3) and ≥7 cancers with 93% accuracy for cancers occurring in both peripheral (PZ) and transition (TZ) zones and 92% for cancers occurring in the PZ alone. Our approach distinguished the GS 7(3+4) from GS 7(4+3) with 92% accuracy for cancers occurring in both the PZ and TZ and with 93% for cancers occurring in the PZ alone. In comparison, a classifier using only the ADC mean achieved a top accuracy of 58% for distinguishing GS 6(3+3) vs. GS ≥7 for cancers occurring in PZ and TZ and 63% for cancers occurring in PZ alone. The same classifier achieved an accuracy of 59% for distinguishing GS 7(3+4) from GS 7(4+3) occurring in the PZ and TZ and 60% for cancers occurring in PZ alone. Separate analysis of the cancers occurring in TZ alone was not performed owing to the limited number of samples. Our results suggest that texture features derived from ADC and T2-w MRI together with sample augmentation can help to obtain reasonably accurate classification of Gleason patterns.

Bone Metastases in Castration-Resistant Prostate Cancer: Associations between Morphologic CT Patterns, Glycolytic Activity, and Androgen Receptor Expression on PET and Overall Survival

PURPOSE To compare the features of bone metastases at computed tomography (CT) to tracer uptake at fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and fluorine 18 16β-fluoro-5-dihydrotestosterone (FDHT) PET and to determine associations between these imaging features and overall survival in men with castration-resistant prostate cancer. MATERIALS AND METHODS This is a retrospective study of 38 patients with castration-resistant prostate cancer. Two readers independently evaluated CT, FDG PET, and FDHT PET features of bone metastases. Associations between imaging findings and overall survival were determined by using univariate Cox proportional hazards regression. RESULTS In 38 patients, reader 1 detected 881 lesions and reader 2 detected 867 lesions. Attenuation coefficients at CT correlated inversely with FDG (reader 1: r = -0.3007; P < .001; reader 2: r = -0.3147; P < .001) and FDHT (reader 1: r = -0.2680; P = .001; reader 2: r = -0.3656; P < .001) uptake. The number of lesions on CT scans was significantly associated with overall survival (reader 1: hazard ratio [HR], 1.025; P = .05; reader 2: HR, 1.021; P = .04). The numbers of lesions on FDG and FDHT PET scans were significantly associated with overall survival for reader 1 (HR, 1.051-1.109; P < .001) and reader 2 (HR, 1.026-1.082; P ≤ .009). Patients with higher FDHT uptake (lesion with the highest maximum standardized uptake value) had significantly shorter overall survival (reader 1: HR, 1.078; P = .02; reader 2: HR, 1.092; P = .02). FDG uptake intensity was not associated with overall survival (reader 1, P = .65; reader 2, P = .38). CONCLUSION In patients with castration-resistant prostate cancer, numbers of bone lesions on CT, FDG PET, and FDHT PET scans and the intensity of FDHT uptake are significantly associated with overall survival.

Type II endoleaks after endovascular repair of abdominal aortic aneurysms: fate of the aneurysm sac and neck changes during long-term follow-up.

Purpose To evaluate the frequency of type II endoleaks after endovascular aneurysm repair (EVAR) and to compare sac diameter and neck changes in patients with type II endoleak to endoleak-free patients with at least 3-year imaging follow-up. Methods Among 407 consecutive EVAR patients, 109 patients (101 men; mean age 72.1 years, range 55–86) had at least 3-year computed tomography (CT) data and no type I or III endoleak. In this cohort, 49 patients presented with a type II endoleak at some time and 60 patients had no endoleak. Patients with type II endoleaks were further divided into subgroups based on the vessel origin and the perfusion status (persistent or transient). The course of the perfusion status of type II endoleaks and changes in the aneurysm sac diameters, neck diameters, and renal to stent-graft distances (RSD) were evaluated in the defined groups. Reintervention and death rates were also reported. Results The mean follow-up was 68.1±23.8 months. Compared to the no endoleak group, overall sac diameter increased significantly in the type II endoleak group (p=0.007), but vessel origin did not have any influence. With regard to the perfusion status of type II endoleaks, aneurysm sac changes were significantly higher (p = 0.002) in the persistent endoleak group. During the study period, the increase in the proximal neck diameter was significantly higher in the no endoleak group compared to the type II endoleak group (p=0.025). No significant difference was found in RSD changes between the defined groups. Reinterventions were performed in 20 (18.3%) patients (13 for type II endoleak); 2 (1.8%) patients without type II endoleak died of ruptured aneurysm. Conclusion Persistent type II endoleaks led to significant aneurysm sac enlargement, but without increased mortality or rupture rates.

Molecular Imaging of Prostate Cancer.

Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls.

Noninvasive Differentiation of Simple Steatosis and Steatohepatitis by Using Gadoxetic Acid–enhanced MR Imaging in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study

PURPOSE To determine whether gadoxetic acid-enhanced magnetic resonance (MR) imaging can be used to distinguish between simple steatosis and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD), defined according to the steatosis activity and fibrosis (SAF) scoring system, which is based on the semiquantitative scoring of steatosis activity and liver fibrosis. MATERIALS AND METHODS The local institutional review committee approved this study and waived written informed consent. This was a retrospective study of gadoxetic acid-enhanced 3-T MR imaging performed in 81 patients with NAFLD (45 men [56%]; mean age, 56 years; range, 25-78 years). The MR images were analyzed by using the relative enhancement (the ratio of signal intensities of the liver parenchyma before and 20 minutes after intravenous administration of gadoxetic acid). Univariate and multiple regression analyses were applied to identify variables associated with relative enhancement measurements. The ability of relative enhancement to allow differentiation between simple steatosis and NASH was assessed by using area under the receiver operating characteristic (ROC) curve analysis. RESULTS Relative enhancement negatively correlated with the degree of lobular inflammation (r = -0.59, P < .0001), ballooning (r = -0.44, P < .0001), and fibrosis (r = -0.59, P ≤ .0001), but not with steatosis (r = -0.16, P = .15). Patients with NASH had a significantly lower relative liver enhancement (0.82 ± 0.22) than those with simple steatosis (1.39 ± 0.52) (P < .001). Relative enhancement measurements performed well in the differentiation between simple steatosis and NASH, with an area under the ROC curve of 0.85 (95% confidence interval: 0.75, 0.91) (cutoff = 1.24, sensitivity = 97%, specificity = 63%). CONCLUSION Gadoxetic acid relative enhancement was significantly lower in patients with NASH than in patients with simple steatosis, but further prospective studies are warranted.

Liver Transplantation: Impaired Biliary Excretion of Gadoxate Is Associated With an Inferior 1-year Retransplantation-free Survival

ObjectivesThe aim of this study was to evaluate gadoxate-enhanced magnetic resonance imaging (MRI) in liver transplant recipients with regard to graft function and mortality at 1 year from imaging. Material and MethodsThis was a retrospective, proof-of-concept study of gadoxate-enhanced 3-T MRI in 51 patients with orthotopic liver transplantation. Relative liver enhancement was calculated as the ratio between the signal intensities in unenhanced and gadoxate-enhanced T1-weighted gradient echo sequences with fat saturation. Impaired excretion was defined as the absence of gadoxate visualization in the common bile duct 20 minutes after intravenous injection. ResultsOf the 51 liver transplant recipients, 31 patients showed a normal hepatobiliary excretion of gadoxate after 20 minutes (group A), whereas 20 patients showed an impaired excretion (group B). Group B had significantly higher serum levels of bilirubin (P < 0.001), aspartate-aminotransferase (P = 0.003), and alkaline phosphatase (P = 0.007), and a higher median Model for End-Stage Liver Disease score (P < 0.001). Within one-year of MRI, 55% of group B died (n = 7) or had to undergo retransplantation (n = 4), whereas all patients in group A survived without retransplantation (P < 0.001). The relative liver enhancement 20 minutes after gadoxate injection was directly related to serum levels of cholinesterase (P < 0.001) and inversely related to the serum levels of bilirubin (P = 0.0098), aspartate-aminotransferase (P = 0.007), and the Model for End-Stage Liver Disease score (P < 0.001). The relative liver enhancement 20 minutes after contrast injection was directly related to the probability of 1-year retransplantation-free survival in proportional hazard regression analysis (P = 0.005). ConclusionGadoxate-enhanced MRI may be a helpful noninvasive prognostic biomarker for chronic rejection and increased risk for 1-year mortality or retransplantation.OBJECTIVES The aim of this study was to evaluate gadoxate-enhanced magnetic resonance imaging (MRI) in liver transplant recipients with regard to graft function and mortality at 1 year from imaging. MATERIAL AND METHODS This was a retrospective, proof-of-concept study of gadoxate-enhanced 3-T MRI in 51 patients with orthotopic liver transplantation. Relative liver enhancement was calculated as the ratio between the signal intensities in unenhanced and gadoxate-enhanced T1-weighted gradient echo sequences with fat saturation. Impaired excretion was defined as the absence of gadoxate visualization in the common bile duct 20 minutes after intravenous injection. RESULTS Of the 51 liver transplant recipients, 31 patients showed a normal hepatobiliary excretion of gadoxate after 20 minutes (group A), whereas 20 patients showed an impaired excretion (group B). Group B had significantly higher serum levels of bilirubin (P < 0.001), aspartate-aminotransferase (P = 0.003), and alkaline phosphatase (P = 0.007), and a higher median Model for End-Stage Liver Disease score (P < 0.001). Within one-year of MRI, 55% of group B died (n = 7) or had to undergo retransplantation (n = 4), whereas all patients in group A survived without retransplantation (P < 0.001). The relative liver enhancement 20 minutes after gadoxate injection was directly related to serum levels of cholinesterase (P < 0.001) and inversely related to the serum levels of bilirubin (P = 0.0098), aspartate-aminotransferase (P = 0.007), and the Model for End-Stage Liver Disease score (P < 0.001). The relative liver enhancement 20 minutes after contrast injection was directly related to the probability of 1-year retransplantation-free survival in proportional hazard regression analysis (P = 0.005). CONCLUSION Gadoxate-enhanced MRI may be a helpful noninvasive prognostic biomarker for chronic rejection and increased risk for 1-year mortality or retransplantation.

Improved Survival After Abdominal Aortic Aneurysm Rupture by Offering Both Open and Endovascular Repair

BACKGROUND In the treatment of ruptured abdominal aortic aneurysm (rAAA), the results of open graft replacement (OGR) have remained constant but discouraging for the last 4 decades. Provided suitable anatomy, elective endovascular abdominal aortic aneurysm repair (EVAR) is less invasive and leads to improved perioperative mortality. Thus, it is reasonable to assume that endovascular treatment should improve the results of rAAA therapy. OBJECTIVE To determine whether the use of both endovascular and open repair of rAAA leads to improved results. DESIGN A single-center, retrospective analysis of 89 patients suffering from rAAA treated either by EVAR or OGR. PATIENTS From October 1999 until July 2006, a consecutive series of patients with rAAA were analyzed. Time was divided into 2 periods of 41 months. During the first period, 42 patients were treated by OGR exclusively. Period 2 started with the availability of an EVAR protocol to treat rAAA; 31 patients received open repair while 16 patients underwent EVAR. MAIN OUTCOME MEASURES Kaplan-Meier survival estimates were calculated and compared. RESULTS Survival estimates showed a statistically significant reduction in overall postoperative mortality following the introduction of EVAR (P < .03). The 90-day overall mortality rate was reduced from 54.8% to 27.7% during the second period (P < .01). Survival of patients older than 75.5 years was especially improved (75% vs 28.6%; P < .01). There was a parallel pattern of significant reduction of the mortality rate after OGR to 29% (P < .03). CONCLUSION Offering both EVAR and OGR to patients with rAAA leads to significant improvements in postoperative survival.

Use of DWI in the Differentiation of Renal Cortical Tumors

OBJECTIVE The purpose of this study was to differentiate clear cell renal cell carcinoma (RCC) from other common renal cortical tumors by use of DWI. MATERIALS AND METHODS The study included 117 patients (mean age, 60 years) with 122 histopathologically confirmed renal cortical tumors who underwent 1.5-T MRI that included DWI before they underwent nephrectomy between 2006 and 2013. For each tumor, two radiologists independently evaluated apparent diffusion coefficient (ADC) values on the basis of a single ROI in a nonnecrotic area of the tumor and also by assessment of the whole tumor. The concordance correlation coefficient (CCC) was calculated to assess interreader agreement. The mean ADC values of clear cell RCC and every other tumor subtype were compared using an exact Wilcoxon rank sum test. RESULTS Interreader agreement was excellent and higher in whole-tumor assessment (CCC, 0.982) than in single-ROI analysis (CCC, 0.756). For both readers, ADC values for clear cell RCC found on single-ROI assessment (2.19 and 2.08 × 10(-3) mm(2)/s) and whole-tumor assessment (2.30 and 2.32 × 10(-3) mm(2)/s) were statistically significantly higher than those for chromophobe, papillary, or unclassified RCC (p < 0.05) but were similar to those for oncocytoma found on single-ROI assessment (2.14 and 2.32 × 10(-3) mm(2)/s) and whole-tumor assessment (2.38 and 2.24 × 10(-3) mm(2)/s). ADC values were also higher for clear cell RCC than for angiomyolipoma, but the difference was statistically significant only in whole-tumor assessment (p < 0.03). CONCLUSION ADC values were statistically significantly higher for clear cell RCC than for chromophobe, papillary, or unclassified RCC subtypes; however, differentiating clear cell RCC from oncocytoma by use of DWI remains especially challenging, because similar ADC values have been shown for these two tumor types.

Endografting increases total volume of AAA repairs but not at the expense of open surgery: experience in more than 1000 patients.

Purpose: To compare the volume of open graft replacements (OGR) for abdominal aortic aneurysm (AAA) versus endovascular aneurysm repairs (EVAR) over time and after modifying selection criteria. Methods: A review was conducted of 1021 consecutive patients who underwent AAA repair from 1989 through 2002: 496 elective OGRs for infrarenal AAAs (STANDARD), 289 elective EVARs for infrarenal AAAs, 59 complex OGRs for suprarenal AAAs, and 177 emergent OGRs for ruptured AAAs. Patients from 1995 to 2002 were divided into 2 groups based on shifting treatment strategies; 454 patients were treated by STANDARD or EVAR at the surgeons discretion between 1995 and 2000 (post EVAR). The second group comprised 161 patients treated in 2001–2002 after the introduction of “high-risk” screening criteria (age ≥72 years, diabetes mellitus, renal dysfunction, impaired pulmonary function, or ASA class IV) that dictated EVAR whenever anatomically feasible. For comparison, 170 STANDARD repairs performed in the 6 years prior to EVAR served as a control. Results: While surgery for ruptured AAAs remained fairly stable over the 14-year period, the number of patients undergoing elective repair increased due to the implementation of EVAR. During the 6 years after its introduction, EVAR averaged 34.3 patients per year; after 2001, the annual frequency of EVAR increased to 41.5 (p>0.05). In like fashion, the rate of STANDARD repairs increased to 41.3 patients per year versus 28.3 before EVAR (p=0.032). ASA class IV patients increased by almost 9 fold in the recent period versus pre EVAR (p= 0.006). The overall mortality after elective infrarenal AAA repair decreased between the pre and post EVAR periods (6.5% versus 3.7%, p>0.05) and fell still further to 1.2% in the most recent period (p=0.021 versus pre EVAR). Conclusions: The implementation of an EVAR program increases the total volume of AAA repairs but does not reduce open surgical procedures. By allocating patients to EVAR or open repair based their risk factors, mortality was markedly reduced.

Effect of body armor on simulated landmine blasts to cadaveric legs.

BACKGROUND Antipersonnel landmine protective footwear relies on blast deflection or on exaggerated standoff between the foot and the explosive. Neither design has been tested for clinical effectiveness. METHODS 4 cadaveric lower extremities--3 fitted with a Koflach boot incorporating TABRE (Technology for Attenuating Blast Related Energy) were subjected to controlled blast with charges of up to 100 g trinitrotoluene (TNT). The blasts were recorded by a digital recording system. All legs were X-rayed and underwent computed tomography scanning before and after testing. RESULTS TABRE-protected limbs directly subjected to the blast hyperextended at the knee during firing. Injuries showed a pattern of open tibial fractures (Gustilo grade I, II), of multiple calcaneal (Sanders Type III, IV), and fibular fractures and of the tibial plateau, but showed no traumatic amputation. CONCLUSIONS Development of protective footwear against landmine blast is feasible. From medium mines up to charges of 100 g TNT limb salvage may be possible.