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Background: We investigated the tumor suppression effect of an ultrasound-sensitive doxorubicin-loaded liposome-based nanoparticle, IMP301, to enhance the synergistic effect with focused ultrasound (FUS) in an animal model of pancreatic cancer., Methods: Thirty nude mice with xenografts of PANC-1 human pancreatic cancer cells were randomly and prospectively allocated to 6 different groups (5 per group) each for Study-1 (dose-response test) and Study-2 (synergistic effect test). Study-1 consisted of control, gemcitabine, Doxil with FUS, and three different doses of IMP301 (2, 4, 6 mg/kg) with FUS groups. Study-2 consisted of control, FUS only, gemcitabine, Doxil with FUS, and IMP301 (4 mg/kg) with or without FUS groups. Differences in tumor volume and growth rate were evaluated by one-way ANOVA and Student-Newman-Keuls test., Results: In Study-1, 4 mg/kg or greater IMP301 with FUS groups showed lower tumor growth rates of 14 ± 4 mm 3 /day (mean ± standard deviation) or less, compared to the control, gemcitabine, and Doxil with FUS groups with rates exceeding 28 ± 5 (p < 0.050). The addition of FUS in Study-2 decreased the tumor growth rate in the IMP301-treated groups from 36 ± 17 to 9 ± 6, which was lower than the control, FUS only, gemcitabine, and Doxil with FUS groups (p < 0.050)., Conclusions: IMP301 combined with FUS exhibited higher tumor growth suppression compared to the use of a conventional drug alone or the combination with FUS. The present study showed the potential of IMP301 to enhance the synergistic effect with FUS for the treatment of pancreatic cancer., Relevance Statement: This article aims to evaluate the synergistic effect of FUS and ultrasound-responsive liposomal drug in tumor growth suppression by using xenograft mouse model of pancreatic ductal adenocarcinoma. FUS-induced ultrasound-sensitive drug release may be a potential noninvasive repeatable treatment option for patients with locally advanced or unresectable pancreatic cancer., Key Points: • Modification of conventional drugs combined with FUS would maximize tumor suppression. • IMP301 with FUS had higher tumor suppression effect compared to conventional chemotherapy. • This image-guided drug delivery would enhance therapeutic effects of systemic chemotherapy., (© 2024. The Author(s).)

Purpose: To evaluate the usefulness of prostate health index (PHI) as an indicator for recommending magnetic resonance imaging (MRI) in patients with prostate-specific antigen (PSA) gray zone level < 10 ng/mL., Methods: 443 patients who underwent prostate biopsy (PB) after serum PHI test and MRI between April 2019 and December 2022 were enrolled. For patients with visible lesion on MRI with Prostate Imaging Reporting and Data System Score (PI-RADS) ≥ 3, MRI-targeted PB was performed in addition to systematic 12-core PB., Results: The optimal cutoff value of PHI for predicting PI-RADS ≥ 3 lesions was 39.6, which was significantly associated with overall prostate cancer (OR 3.07, p = 0.018) and clinically significant prostate cancer (csPCa) (OR 4.15, p = 0.006) at MRI-targeted PB cores. When MRI was restricted to patients with PHI ≥ 39.6 alone, 28.7% of unnecessary MRI could be saved at the cost of missing 13.6% of csPCa. When omitting MRI for patients with PHI < 39.6 and PSAD < 0.12 ng/mL 2 , unnecessary MRI could be reduced by 20.1% with the risk of missing 6.2% of csPCa. With addition of systematic PB, 21.0% of patients with negative MRI-targeted PB were diagnosed as csPCa., Conclusions: For patients in PSA gray zone, PHI of 39.6 might be an indicator for MRI and further MRI-targeted PB in additional to PSAD of 0.12 ng/mL 2 , reducing 20.1% of unnecessary MRI with the minimal risk of missing 6.2% of csPCa. To maximize csPCa detection, combining both MRI-targeted and systematic PB should be also considered., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To evaluate the diagnostic performance of the tumor contact length (TCL) in the prediction of MIBC (muscle-invasive bladder cancer) in lesions corresponding to the vesical imaging-reporting and data system (VIRADS) score 2-3., Methods: This is a single institution, retrospective study targeting 191 consecutive patients assigned of VIRADS score 2-3, who had pre-transurethral resection MRI from July 2019 to September 2021. Logistic regression analyses were performed to determine meaningful predictors of MIBC for this score group, and a nomogram was plotted with those variables. The diagnostic performance of each predictor was compared at predefined thresholds (VIRADS score 3 and TCL 3 cm) using the generalized linear model and ROC analysis., Results: Both VIRADS score and TCL remained independent predictors of MIBC for this score group (odds ratio 7.3 for VIRADS score, and 1.3 for TCL, p < 0.01 for both). The contribution of TCL to the probability of MIBC in the nomogram was greater than that of the VIRADS score. VIRADS score had a sensitivity of 0.54 (14/26), specificity of 0.92 (203/221), and diagnostic accuracy of 0.88 (217/247), and TCL showed a sensitivity of 0.89 (23/26), specificity of 0.95 (209/221), and diagnostic accuracy of 0.94 (232/247). The difference in sensitivity (p = 0.03) and accuracy (p = 0.04) was statistically significant. The AUC was also significantly wider for TCL than for VIRADS (0.97 vs. 0.73, p < 0.01)., Conclusion: A simple index, TCL, may be helpful in further risk stratification for MIBC in patients with a score of VIRADS 2-3., Clinical Relevance Statement: For bladder cancer patients with insufficient qualitative evidence of muscle layer invasion using VIRADS categorization, TCL, a simple quantitative indicator defined as the curvilinear contact length between the bladder wall and the tumor, may be helpful in risk stratification., Key Points: • Even when only lesions with score 2-3 were targeted, VIRADS was still a meaningful indicator of MIBC. • With a predefined threshold of 3 cm applied, TCL outperformed VIRADS in the score 2-3 group, in predicting MIBC. • A longer TCL for a lesion with a VIRADS score 2 may warrant an additional warning for MIBC, whereas a shorter TCL for a lesion with a score 3 may indicate a lower risk of MIBC., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: To evaluate association between computer tomography (CT)-based features of renal cell carcinoma (RCC) and survival outcomes., Methods: Data of 958 patients with clinical T1b-T2 RCC who underwent partial/radical nephrectomy from June 2003 to March 2022 were retrospectively evaluated. CT images of patients were reviewed by two radiologists for texture analysis of tumor heterogeneity and shape analysis of tumor contour. Patients were divided into three groups according to patterns of CT-based features: (1) favorable feature group (n = 117); (2) intermediate feature group (n = 606); and (3) unfavorable feature group (n = 235). Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed to evaluate overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS)., Results: RCCs with unfavorable CT-based feature showed larger size on CT, higher nuclear grade, higher rate of histologic necrosis, and higher rate of capsular invasion than those in the other two groups (all p < 0.001). Unfavorable feature was associated with poorer OS (p = 0.001), CSS (p < 0.001), and RFS (p < 0.001) on Kaplan-Meier analysis. In multivariate analysis, intermediate and unfavorable features were independent predictors for recurrence (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.09-5.79, p = 0.031 and HR 3.71, 95% CI 1.58-8.73, p = 0.003, respectively), but not for overall death or RCC-specific death., Conclusions: A combination of irregular tumor contour feature with heterogeneous tumor texture feature on CT is associated with poor RFS in clinical T1b-T2 RCC preoperatively., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The objective of this study was to evaluate pain and image quality associated with the use of two different ultrasound transducers., Methods: Fifty healthy male participants aged 30 years or older were prospectively enrolled. All ultrasound procedures were performed using a V8 machine (Samsung Medison, Seoul, Korea) equipped with EA2-11 (conventional) and miniER7 (small-caliber) transrectal transducers, operated by a single genitourinary radiologist. To minimize bias, one group of volunteers underwent ultrasonography with the conventional transducer first, followed by the small transducer. For the remaining participants, the examinations were performed in the opposite order. Ultrasonography, including the measurement of total prostate and transitional zone volumes, was conducted in accordance with standard practice. After testing with both probes, participants were asked to rate their pain on a 10-point numerical rating scale (NRS). A radiologist then evaluated the quality of the images acquired with each probe using a 5-point numeric scale and compared the prostate volume measurements obtained by each method., Results: The mean NRS scores associated with the conventional and small transducers were 4.7±1.8 and 2.7±1.2, respectively (P<0.05). The mean ultrasound image qualities from the two transducers were statistically similar (4.78 and 4.74, P>0.05). The whole prostate gland volume as measured with the conventional transducer (mean±standard deviation, 24.2±9.1 mL) was greater than the measurement (22.1±8.7 mL) obtained with the small-caliber transducer (P<0.05). However, only two of the 50 whole gland volume measurements differed by more than two standard deviations., Conclusion: The use of a small transrectal probe significantly reduced pain without compromising image quality.

Conventional chemotherapy methods have adverse off-target effects and low therapeutic efficiencies of drug release in target tumors. In this study, we proposed a combination therapy of doxorubicin (DOX)-loaded ultrasound (US)-sensitive liposomal nanocarriers (IMP301), microbubbles (MBs) under focused US exposure using convex acoustic lens-attached US (LENS) to tumor treatment. The therapeutic effects of each treatment in a murine melanoma model were evaluated using contrast-enhanced US (CEUS) and micro-computed tomography (micro-CT) imaging, bioluminescence and confocal microscopy imaging, and liquid chromatography-mass spectroscopy (LC/MS) analysis. Tumor-bearing mice were randomly assigned to one of the following groups: (1) G1: IMP301 only (n = 9); (2) G2: IMP301 + LENS (n = 9); (3) G3: IMP301 + MB + LENS (n = 9); (4) G4: DOXIL only (n = 9); and (5) G5: IMP301 without DOXIL group as a control group (n = 4). Ten days after tumor injection, tumor-bearing mice were treated according to each treatment strategy on 10th, 12th, and 14th days from the day of tumor injection. The CEUS images of the tumors in the murine melanoma model clearly showed increased echo signal intensity from MBs as resonant US scattering. The relative tumor volume of the G2 and G3 groups on the micro-CT imaging showed inhibited tumor growth than the reference baseline of the G5 group. DOX signals on bioluminescence and confocal microscopy imaging were mainly located at the tumor sites. LC/MS showed prominently higher intratumoral DOX concentration in the G3 group than in other treated groups. Therefore, this study effectively demonstrates the feasibility of the synergistic combination of IMP301, MBs, and LENS-application for tumor-targeted treatment. Thus, this study can enable efficient tumor-targeted treatment by combining therapy such as IMP301 + MBs + LENS-application., (© 2023. Springer Nature Limited.)

Purpose: This article aims to evaluate the pooled diagnostic performance control MRI for prediction of recurrent prostate cancer (PCa) after high-intensity focused ultrasound (HIFU)., Materials and Methods: MEDLINE, EMBASE, and Cochrane library databases up to December 31, 2021, were searched. We included studies providing 2×2 contingency table for diagnostic performance of MRI in predicting recurrent PCa after HIFU, using control biopsy as reference standard. The quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Sensitivity and specificity were pooled and displayed in a summary receiver operating characteristics (SROC) plot. Meta-regression analysis using clinically relevant covariates was performed for the causes of heterogeneity., Results: Nineteen studies (703 patients) were included. All included studies satisfied at least four of the seven QUADAS-2 domains. Pooled sensitivity was 0.81 (95% CI 0.72-0.90) with specificity of 0.91 (95% CI 0.86-0.96), with area under the SROC curve of 0.81. Larger studies including more than 50 patients showed relatively poor sensitivity (0.68 vs. 0.84) and specificity (0.75 vs. 0.93). The diagnostic performance of studies reporting higher nadir serum prostate-specific antigen levels (>1 ng/mL) after HIFU was inferior, and differed significantly in sensitivity (0.54 vs. 0.78) rather than specificity (0.85 vs. 0.91)., Conclusions: Although MRI showed adequate diagnostic performance in predicting PCa recurrence after HIFU, these results may have been exaggerated., Competing Interests: The authors have no conflicts of interest., (© 2023 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

Purpose: To evaluate the diagnostic performance of follow-up multiparametric MRI for prediction of recurrent prostate cancer after high-intensity focused ultrasound (HIFU), and to find other, if any, clinical or radiological predictors., Materials and Methods: Post-HIFU MRIs of 110 consecutive patients who underwent follow-up biopsies between August 2019 and April 2021 were retrospectively analyzed and the likelihood of recurrence was assessed on a five-point Likert scale by two board-certified uroradiologists. Diagnostic performance of the Likert scale assigned to the post-HIFU MRI was assessed using the follow-up biopsy results as a reference standard. Among the clinical and radiological variables, predictors of the recurrence were examined through logistic regression., Results: In per-patient and per-sector analyses, Likert scale on post-HIFU MRI showed a sensitivity and specificity of 0.37 and 0.97, and 0.42 and 0.87, respectively, in predicting recurrence. Two patients with high suspicion on MRI required additional treatment to regain biochemical control despite negative biopsies. High suspicion on post-HIFU MRI (odds ratio = 1.74; p < 0.01), and more cancer-positive cores on initial biopsy (odds ratio = 1.25; p = 0.03) were independent predictors of recurrence., Conclusion: Albeit with low sensitivity, high suspicion on post-HIFU MRI may be clinically important because of its high specificity, especially when considering the possibility of sampling error in biopsies. Patients with a high number of cancer-positive cores at diagnosis should avoid HIFU as they have an increased risk of recurrence., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: The aim of this study was to evaluate the effectiveness of the Prostate Health Index (PHI) and prostate multi-parametric magnetic resonance imaging (mpMRI) in predicting prostate cancer (PCa) and clinically significant prostate cancer (csPCa) during initial prostate biopsy., Materials and Methods: In total, 343 patients underwent initial prostate biopsy and were screened by use of PHI and prostate-specific antigen (PSA) levels between April 2019 and July 2021. A subgroup of 232 patients also underwent prostate mpMRI. Logistic regression analysis was performed to evaluate the accuracies of PSA, PHI, and mpMRI as predictors of PCa or csPCa. These predictive accuracies were quantified by using the area under the receiver operating characteristic curve. The different predictive models were compared using the DeLong test., Results: Logistic regression showed that age, PSA, PHI, and prostate volume were significant predictors of both PCa and csPCa. In the mpMRI subgroup, age, PSA level, PHI, prostate volume, and mpMRI were predictors of both PCa and csPCa. The PHI (area under the curve [AUC]=0.693) was superior to the PSA level (AUC=0.615) as a predictor of PCa (p=0.038). Combining PHI and mpMRI showed the most accurate prediction of both PCa and csPCa (AUC=0.833, 0.881, respectively)., Conclusions: The most accurate prediction of both PCa and csPCa can be performed by combining PHI and mpMRI. In the absence of mpMRI, PHI is superior to PSA alone as a predictor of PCa, and adding PHI to PSA can increase the detection rate of both PCa and csPCa., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

We aimed to compare the complications and pathological outcomes between systematic 12-core transrectal ultrasonography guided prostate biopsy (TRUS-PB) and magnetic resonance imaging-TRUS fusion targeted prostate biopsy (MRI-TRUS FTPB). We examined 10,901 patients who underwent prostate biopsy from May 2003 to December 2017 retrospectively. Among them, 10,325 patients underwent 12-core TRUS-PB and 576 patients underwent MRI-TRUS FTPB. The clinicopathological features and complications in both groups were compared. After propensity score matching, there were no significant differences in the clinical features and complication rates between both groups (P > .05). In the multivariate analyses, the prostate volume was shown to be the only significant predictor of overall complications, infectious complications, bleeding related complications, and Clavien-Dindo grade ≥ 2 complications after prostate biopsy (P < .001). The present study demonstrates the safety of MRI-TRUS FTPB in terms of complications, compared with that of TRUS-PB. Although the combination of MRI-TRUS FTPB and 12-core TRUS-PB provides enhanced diagnostic power, MRI-TRUS FGB alone could provide a reasonable diagnostic value for prostate cancer if the apparent diffusion coefficient suspicious grade of prostate cancer is ≥4. When the Likert suspicious grade of prostate cancer on the apparent diffusion coefficient map of multiparametric MRI was 3, 13.9% (27/194) of the patients were diagnosed with clinically significant prostate cancer (csPCa); 44.4% (12/27) of them were confirmed as csPCa at the MRI-targeted cores. When the apparent diffusion coefficient suspicious grade was ≥4, 43.0% (108/251) were diagnosed with csPCa; 76.8% (83/108) of them were confirmed to have csPCa at the MRI-targeted cores., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Glioblastoma is considered one of the most aggressive and dangerous brain tumors. However, treatment of GBM has been still challenged due to blood-brain barrier (BBB). BBB prevents that the chemotherapeutic molecules are extravasated to brain. In this study, sonosensitive liposome encapsulating doxorubicin (DOX) was developed for enhancement of GBM penetration in combination with focused ultrasound (FUS) and microbubbles. Upon ultrasound (US) irradiation, microbubbles induce cavitation resulting in the tight junction of BBB endothelium to temporarily open. In addition, the composition of sonosensitive liposome was optimized by comparison of sonosensitivity and intracellular uptake to U87MG cells. The optimal sonosensitive liposome, IMP301-DC, resulted 123.9 ± 38.2 nm in size distribution and 98.2 % in loading efficiency. Related to sonosensitivity of IMP301-DC, US-triggered release ratio of doxorubicin was 69.2 ± 12.3 % at 92 W/cm 2 of US intensity for 1 min. In the in vivo experiments, the accumulation of DiD fluorescence probe labeled IMP301-DC-shell in the brain through the BBB opening was increased more than two-fold compared to that of Doxil-shell, non-sonosensitive liposome. US exposure significantly increased GBM cytotoxicity of IMP301-DC. In conclusion, this study demonstrated that IMP301-DC could serve as an alternative solution to enhance the penetration to GBM treatment via BBB opening by non-invasive FUS combined with microbubbles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Positron emission tomography (PET) using different positron-emitting radiopharmaceuticals has emerged as a promising new metabolic diagnostic tool for the evaluation of a variety of malignant diseases. Thus, we investigated the diagnostic efficacy of F-18-Fluorocholine positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mpMRI) for the detection and localization of tumors within the prostate with the correlating histopathology as the standard of reference., Methods: Forty patients with histologically proven prostate cancer underwent both F-18-Fluorocholine PET/CT and mpMRI before robot-assisted laparoscopic radical prostatectomy (RARP). The maximum standard uptake values and the tumor-to-background ratio were measured on a sextant basis. In brief, the sextants were defined as right apex, right middle, right base, left apex, left middle, and left base. For each tumor region, the correlation of the tumor localization based on the sextant in both F-18-Fluorocholine PET/CT and mpMRI scans with the histopathological results was determined., Results: The correlation between both imaging modalities and RARP pathology representing (1) all cancer and (2) clinically significant cancer defined as a ≥ International Society of Urological Pathology grade of 2 showed that the sensitivity and the area under the curve (AUC) were higher for mpMRI than for F-18-Fluorocholine PET/CT. In contrast, F-18-Fluorocholine PET/CT had relatively higher specificity than mpMRI. Importantly, we found a very high AUC value of over 0.8 in both imaging modalities., Conclusion: mpMRI had results superior to F-18-Fluorocholine PET/CT in assessing intraprostatic tumor localization. However, F-18-Fluorocholine PET/CT showed superiority in terms of specificity. Thus, using both modalities in conjunction could provide better treatment planning., Competing Interests: All authors have no conflicts of interest to disclose., (© 2022 Asian Pacific Prostate Society. Publishing services by Elsevier B.V.)

Purpose: To validate the diagnostic yield of multiparametric magnetic resonance imaging (mpMRI) for local biochemical recurrence after radical prostatectomy in patients with biochemical recurrence using large consecutive patient data., Materials and Methods: Of 4632 patients who underwent radical prostatectomy for prostate adenocarcinoma, 748 patients with prostate-specific antigen > 0.2 ng/mL and second confirmatory level were retrospectively identified. Among them, 468 patients who underwent multiparametric magnetic resonance imaging were analyzed. The primary outcome measure was the diagnostic yield of multiparametric magnetic resonance imaging for local recurrence, and the secondary measure was its accuracy, using the response to salvage radiotherapy as reference., Results: Only 33 patients (7.1%) showed positive imaging findings. The positive and negative predictive values were 84.8% (28/33) and 37.5% (45/120), respectively. The sensitivity and specificity were 27.2% (28/103) and 90% (45/50), respectively. The overall accuracy was 47.7% (73/153). In multivariate logistic regression analysis, prostate-specific antigen level at recurrence was found to be the only factor significantly higher in the positive image findings group., Conclusions: The universal use of multiparametric magnetic resonance imaging resulted in a low-diagnostic yield for local recurrence in patients with biochemical recurrence after radical prostatectomy. The results suggest that selective use of multiparametric magnetic resonance imaging should be considered in patients with a higher prostate-specific antigen threshold., Competing Interests: All authors have no disclosure of any relationship with industry for this study or have no conflict of interest to declare., (© 2022 Asian Pacific Prostate Society. Published by Elsevier B.V.)

Background Guidelines recommending additional imaging for adrenal nodules lack relevant epidemiologic evidence. Purpose To measure the prevalence of adrenal nodules detected at staging CT in patients with potentially resectable gastric cancer and the proportion of patients with malignant nodules among them. Materials and Methods This retrospective study included 10 250 consecutive patients (median age, 63 years; interquartile range, 53-71 years; 6884 men) who underwent staging CT and had potentially resectable gastric cancer in a tertiary center (May 2003 to December 2018). All 10 250 CT studies were retrospectively reviewed, and patients with adrenal nodules (or thickening ≥10 mm) were identified to measure the prevalence of adrenal nodules. Among patients with adrenal nodules, the per-patient proportions of malignant nodules, adrenal metastasis from gastric cancer, and additional adrenal examinations were measured. A secondary analysis was performed by using data from the original CT reports. The same metrics that were used in the retrospective review were assessed. Results The prevalence of adrenal nodules was 4.5% (95% CI: 4.1, 4.9; 462 of 10 250). The proportions of malignant nodules and adrenal metastasis from gastric cancer were 0.4% ( 95% CI: 0.1, 1.6; two of 462) and 0% (95% CI: 0.0, 0.8; 0 of 462), respectively. A total of 27% of the patients (95% CI: 23, 31; 123 of 462) underwent additional adrenal examination. According to original CT reports, the prevalence of adrenal nodules and the proportions of malignant nodules, adrenal metastases from gastric cancer, and additional adrenal examination were 2.7% (95% CI: 2.4, 3.0; 272 of 10 250), 0.7% (95% CI: 0.1, 2.6; two of 272), 0% (95% CI: 0.0, 1.4; 0 of 272), and 42.6% (95% CI: 36.7, 48.8; 116 of 272), respectively. Conclusion Although adrenal nodules were detected frequently on staging CT images of patients with otherwise resectable gastric cancer, these nodules were rarely malignant. ©RSNA, 2021 Online supplemental material is available for this article . See also the editorial by Baumgarten in this issue.

Co-delivery of microbubbles (MBs) with anticancer drugs is a promising theranostic approach that can enhance both the ultrasound contrast and local extravasation of drugs with the sonoporation effect. The simultaneous administration of MBs and hydrophobic drugs, however, is still challenging due to the limitations in drug loading or undesirable stabilization of MBs. In this research, MB-self-aggregate complexes (MB-SAs) were newly fabricated for the encapsulation of hydrophobic drugs, and their theranostic properties are investigated in vitro and in vivo . Glycol chitosan self-aggregates (GC-SAs) loaded with hydrophobic drugs or dyes were chemically conjugated on the surface MBs. Their conjugation ratio was determined to be 73.9%, and GC-SAs on MBs did not affect the stability of MBs. GC-SA attached MBs (GC@MBs) were successfully visualized with low-intensity insonation and showed enhanced cellular uptake via the sonoporation effect. In vivo biodistribution of GC@MBs was examined with tumor-bearing mice, confirming that their accumulation at the tumor site increased by 1.85 times after ultrasound irradiation. The anticancer drug-loaded GC@MBs also exhibited 10% higher cytotoxicity under ultrasound flash. In conclusion, it was expected that GC@MBs could be used both as an ultrasound contrast agent and a drug carrier even with conventional ultrasonic devices.

Purpose: This study aimed to apply doxorubicin-loaded nanoparticle microbubble (Dox-NP-MB) therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) and investigate the utility of contrast-enhanced ultrasound (CEUS) and intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) for response evaluation., Methods: Twenty-eight N1S1 HCC model rats were treated with either Dox-NP-MB (group [G] 1, n=8), doxorubicin (Dox) alone (G2, n=7), nanoparticle microbubbles alone (G3, n=7), or saline (G4, control, n=6) on days 0 and 7, and were sacrificed on day 11. IVIM-DWI and CEUS were performed before each treatment and before euthanasia. Efficacy was estimated by the percentage of tumor volume growth inhibition compared with control. Toxicity was assessed by body weight changes and blood tests. Post-treatment changes in IVIM-DWI and CEUS parameters were analyzed., Results: Tumor volume growth was inhibited by 48.4% and 90.2% in G1 and G2 compared to G4, respectively. Compared to G2, G1 had a significantly lower degree of body weight change (median, 91.0% [interquartile range, 88.5%-97.0%] vs. 88.0% [82.5%-88.8%], P<0.05) and leukopenia (1.75×103 cells/μL [1.53-2.77] vs. 1.20×103 cells/μL [0.89-1.51], P<0.05). After the first treatment, an increase in peak enhancement, wash-in rate, and wash-in perfusion index on CEUS was observed in G3 and G4 but suppressed in G1 and G2; the apparent diffusion coefficients, true diffusion coefficients, and perfusion fractions significantly increased in G1 and G2 compared to baseline (P<0.05)., Conclusion: Dox-NP-MB showed reduced Dox toxicity. Early changes in some CEUS and IVIM-DWI parameters correlated with the therapeutic response.

Photoacoustic (PA) imaging is used widely in cancer diagnosis. However, the availability of PA agents has not made great progress due to the limitations of the one currently in use, porphyrin. Porphyrin-Micelle (PM), developed by synthesizing porphyrin and PEG-3.5k, confirmed the amplification of the PA agent signal, and added binding affinity in an LNCaP model by attaching prostate-specific membrane antigen PSMA. Compared to the previously used porphyrin, a superior signal was confirmed, and the potential of PMP was confirmed when it showed a signal superior to that of hemoglobin at the same concentration. In addition, in the in vivo mouse experiment, it was confirmed that the signal in the LNCaP xenograft model was stronger than that in the PC-3 xenograft model, and the PMP signal was about three times higher than that of PM and porphyrin.

Magnetic resonance imaging (MRI) is increasingly important in the detection and localization of prostate cancer. Regarding suspicious lesions on MRI, a targeted biopsy using MRI fused with ultrasound (US) is widely used. To achieve a successful targeted biopsy, a precise registration between MRI and US is essential. The purpose of our study was to show any decrease in errors using a real-time nonrigid registration technique for prostate biopsy. Nineteen patients with suspected prostate cancer were prospectively enrolled in this study. Registration accuracy was calculated by the measuring distance of corresponding points by rigid and nonrigid registration between MRI and US, and compared for rigid and nonrigid registration methods. Overall cancer detection rates were also evaluated by patient and by core. Prostate volume was measured automatically from MRI and manually from US, and compared to each other. Mean distances between the corresponding points in MRI and US were 5.32 ± 2.61 mm for rigid registration and 2.11 ± 1.37 mm for nonrigid registration ( p < 0.05). Cancer was diagnosed in 11 of 19 patients (57.9%), and in 67 of 266 biopsy cores (25.2%). There was no significant difference in prostate-volume measurement between the automatic and manual methods ( p = 0.89). In conclusion, nonrigid registration reduces targeting errors.

Objective: To identify patients who can safely evade the magnetic resonance imaging fusion-targeted biopsy (MRIFTB) for prostate imaging reporting and data system (PI-RADS) 3 lesion., Materials and Methods: Overall, 755 men with PI-RADS 3-5 lesions who underwent MRIFTB were retrospectively analyzed. Univariate and multivariate analyses were performed to determine significant predictors for clinically significant prostate cancer (CSPCa), defined as Gleason grade group ≥ II. Detection rates and negative predictive values of CSPCa were estimated according to various clinical settings., Results: Median age, prostate-specific antigen (PSA), and PSA density of patients were 66.0 years, 7.39 ng/mL, and 0.19 ng/mL, respectively. Overall detection rates of CSPCa according to PI-RADS 3 (n = 347), 4 (n = 260), and 5 (n = 148) lesions were 15.0%, 30.4%, and 80.4%, respectively. The negative predictive value (NPV) of PI-RADS 3 lesion on MRI was 15.0%. On multivariate analysis, age [≥ 65 years, odds ratio (OR) = 0.427], PSA density (≥ 0.20 ng/mL 2 , OR = 0.234), prior negative biopsy history (OR = 2.231), and PI-RADS score (4, OR = 0.427; 5, OR = 0.071) were independent predictors for the absence of CSPCa by MRIFTB. When assessed according to various conditions, NPVs of PI-RADS 3 lesions were relatively high in subgroups with low PSA density (< 0.20 ng/mL 2 ) regardless of age or prior biopsy history (NPV range 91.1-91.9%). Contrarily, NPVs in subgroups with high PSA density were relatively low and varied according to age or prior biopsy history groups (NPV range 50.0-86.8%)., Conclusions: Men with the PI-RADS 3 lesion and low PSA density might safely evade the MRIFTB, regardless of age or prior biopsy history.

Background: To identify potential prognostic factors among patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6., Methods: From 2003 to 2019, favorable intermediate risk patients who underwent radical prostatectomy were included in this study. All patients were evaluated preoperatively with MRI. Using PI-RADS scores, patients were divided into two groups, and clinic-pathological outcomes were compared. The impact of preoperative factors on significant pathologic Gleason score upgrading (≥ 4 + 3) and biochemical recurrence were assessed via multivariate analysis. Subgroup analysis was performed in patients with PI-RADS ≤ 2., Results: Among the 239 patients, 116 (48.5%) were MRI-negative (PI-RADS ≤ 3) and 123 (51.5%) were MRI-positive (PI-RADS > 3). Six patients in the MRI-negative group (5.2%) were characterized as requiring significant pathologic Gleason score upgrading compared with 34 patients (27.6%) in the MRI-positive group (p < 0.001). PI-RADS score was shown to be a significant predictor of significant pathologic Gleason score upgrading (OR = 6.246, p < 0.001) and biochemical recurrence (HR = 2.595, p = 0.043). 10-years biochemical recurrence-free survival was estimated to be 84.4% and 72.6% in the MRI-negative and MRI-positive groups (p = 0.035). In the 79 patients with PI-RADS ≤ 2, tumor length in biopsy cores was identified as a significant predictor of pathologic Gleason score (OR = 11.336, p = 0.014)., Conclusions: Among the patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6, preoperative MRI was capable of predicting significant pathologic Gleason score upgrading and biochemical recurrence. Especially, the patients with PI-RADS ≤ 2 and low biopsy tumor length could be a potential candidate to active surveillance.

Objectives: To examine the diagnostic performance of Vesical Imaging-Reporting and Data System (VIRADS) and to find a quantitative indicator for predicting muscle layer invasion of bladder cancer., Methods: 3-T MRI of 82 patients performed before transurethral resection of bladder tumors or radical cystectomy between July 2018 and June 2019 were retrospectively analyzed. For one index lesion of each patient, two radiologists independently assigned VIRADS score and measured tumor-wall interface (contact length between tumor and bladder wall) on T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. Inter-reader agreement was assessed, and logistic regression analysis was performed to find indicators of muscle layer invasion. Comparison of indicators' diagnostic performance was done with receiver operating characteristic (ROC) curve and generalized linear model analyses. Optimal cutoff point was determined by the Youden index J., Results: Inter-reader agreement was at least substantial for VIRADS categorization (κ 0.77-0.81), and almost perfect for tumor-wall interface (intraclass correlation coefficient 0.88-0.90). Tumor-wall interface (odds ratio [OR] 1.90-2.00) and VIRADS score (OR 8.59-8.89) were independently associated with muscle layer invasion (p ≤ 0.02). For VIRADS, area under the ROC curve (AUROC) was 0.94, and the accuracy was 0.93 at score 3, the optimal threshold for predicting muscle layer invasion. Depending on the MRI sequence, tumor-wall interface showed AUROCs of 0.90-0.92 and accuracy of 0.84-0.90 at suggested thresholds (3 ± 0.3 cm). Tumor-wall interface showed insignificant differences in accuracy compared with VIRADS (p > 0.10), except as measured on diffusion-weighted images (p = 0.01)., Conclusions: VIRADS is a good predictor of muscle layer invasion. As an independent quantitative indicator, tumor-wall interface may complement VIRADS to enhance prediction., Key Points: • Vesical Imaging-Reporting and Data System (VIRADS) is a promising predictor of muscle invasion of bladder cancer with good reproducibility, as suggested by previous studies. • VIRADS score and the tumor-wall interface (curvilinear contact length between the tumor and the bladder wall) are independent predictors of muscle layer invasion. • As an easy-to-use quantitative indicator, tumor-wall interface is expected to be used as an indicator complementary to VIRADS, a qualitative indicator.

A combined transrectal ultrasound and photoacoustic (TRUS-PA) imaging probe was developed for the clear visualization of morphological changes and microvasculature distribution in the prostate, as this is required for accurate diagnosis and biopsy. The probe consisted of a miniaturized 128-element 7 MHz convex array transducer with 134.5° field-of-view (FOV), a bifurcated optical fiber bundle, and two optical lenses. The design goal was to make the size of the TRUS-PA probe similar to that of general TRUS probes (i.e., about 20 mm), for the convenience of the patients. New flexible printed circuit board (FPCB), acoustic structure, and optical lens were developed to meet the requirement of the probe size, as well as to realize a high-performance TRUS-PA probe. In visual assessment, the PA signals obtained with the optical lens were 2.98 times higher than those without the lens. Moreover, the in vivo experiment with the xenograft BALB/c (Albino, Immunodeficient Inbred Strain) mouse model showed that TRUS-PA probe was able to acquire the entire PA image of the mouse tight behind the porcine intestine about 25 mm depth. From the ex vivo and in vivo experimental results, it can be concluded that the developed TRUS-PA probe is capable of improving PA image quality, even though the TRUS-PA probe has a cross-section size and an FOV comparable to those of general TRUS probes.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary or secondary liver cancer. However, conventional TACE formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. Methods: To overcome these limitations, a doxorubicin-loaded albumin nanoparticle-conjugated microbubble complex in an iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) has been developed as a new ultrasound-triggered TACE formulation. Results: (1) Microbubbles enhanced therapeutic efficacy by effectively delivering doxorubicin- loaded nanoparticles into liver tumors via sonoporation under ultrasound irradiation (US+). (2) Microbubbles constituting the complex retained their function as an ultrasound contrast agent in Lipiodol. In a rabbit VX2 liver cancer model, the in vivo study of DOX-NPs-MB complex in Lipiodol (US+) decreased the viability of tumor more than the conventional TACE formulation, and in particular, effectively killed cancer cells in the tumor periphery. Conclusion: Incorporation of doxorubicin-loaded microbubble in the TACE formulation facilitated drug delivery to the tumor with real-time monitoring and enhanced the therapeutic efficacy of TACE. Thus, the enhanced TACE formulation may represent a new treatment strategy against liver cancer., Competing Interests: Competing Interests: Hyungwon Moon and Hak Jong Lee are part of the IMGT Company that is behind the new concept of TACE formulation reported in this study. Hyuncheol Kim and JinWook Chung are shareholders of IMGT Company. The remaining authors have no competing interests to declare., (© The author(s).)

Cancer immunotherapy has revolutionized the way different neoplasms are treated. Among the different variations of cancer immunotherapy, the checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis have been validated and are currently used in the clinics. Nevertheless, these therapeutic antibodies are associated with significant side effects and are known to induce immune-related toxicities. To address these issues, we have developed an immune-microbubble complex (IMC) which not only reduces the toxicities associated with the antibodies but also enhances the therapeutic efficacy when combined with focused ultrasound. The concept of IMCs could be applied to any type of antibody-based treatment regimens to maximize their therapeutic potential.

Purpose: To assess the feasibility of the combined sorafenib (SOR) and doxorubicin-loaded microbubble-albumin nanoparticle complex (DOX-MAC) treatment effect in an orthotopic rat model of hepatocellular carcinoma (HCC)., Materials and Methods: Sixty-two rats with N1-S1 hepatoma were divided into four groups according to the treatment methods, i.e. G1 (SOR and DOX-MAC; n = 12), G2 (SOR; n = 15), G3 (DOX-MAC; n = 12), G4 (DOX; n = 11), and G5 (normal saline; n = 12). We performed the theragnostic, contrast-enhanced ultrasound examination and treatment at the baseline, one-week, and two-weeks. Tumor volume and perfusion parameters were compared at each time point and the differences between all of the groups over time were analyzed using repeated measures ANOVA. We also analyzed the apoptotic index and microvessel density (MVD) per each tumor specimen in all of the groups., Results: The tumors increased from the beginning in all of the groups to the final follow-up, whereas the tumor growth in the G1 group and the G2 group was inhibited during the treatment period compared to the baseline tumor volume (P = 0.016 and P = 0.031). The G1 group resulted in tumor growth inhibition compared to the control group (P = 0.008). The G1 group showed that the peak enhancement and wash-in area under the curve were lower than that of the G4 group (P = 0.010 and 0.022). However, there was no difference in perfusion parameters in the other treated group compared to control group. The MVD of the G1 group tumor was lower than that of the G4 group (P = .016)., Conclusion: Our results suggest that the combination therapy of SOR and DOX-MAC can cause inhibition of tumor growth after treatment and that this therapy can be adequately monitored using the theragnostic DOX-MAC agent., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: S.L. Activities related to the present article: disclosed no relevant relationships. J.H.K. Activities related to the present article: disclosed no relevant relationships. H.M. disclosed no relevant relationships. H.J.L. disclosed no relevant relationships. Competing interest of all authors does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Biparametric (bp) magnetic resonance imaging (MRI) could be an alternative MRI for the detection of the clinically significant prostate cancer (csPCa)., Purpose: To compare the accuracies of prostate cancer detection and localization between prebiopsy bpMRI and postbiopsy multiparametric MRI (mpMRI) taken on different days, using radical prostatectomy specimens as the reference standards., Material and Methods: Data of 41 total consecutive patients who underwent the following examinations and procedures between September 2015 and March 2017 were collected: (1) magnetic resonance- and/or ultrasonography-guided biopsy after bpMRI; (2) postbiopsy mpMRI; and (3) radical prostatectomy with csPCa. Two radiologists scored suspected lesions on bpMRI and mpMRI independently using Prostate Imaging Reporting and Data System version 2. The diagnostic accuracy of detecting csPCa and the Dice similarity coefficient were obtained. Apparent diffusion coefficient (ADC) ratios were also obtained for quantitative comparison between bpMRI and mpMRI., Results: Diagnostic accuracies on bpMRI and mpMRI were 0.83 and 0.82 for reader 1; 0.80 and 0.82 for reader 2. There are no significantly different values of diagnostic sensitivities or specificities between the readers or between MRI protocols. Intra-observer Dice similarity coefficient was significantly lower in reader 2, compared to that in reader 1 between the two MRI protocols. The range of mean ADC ratio was 0.281-0.635. There was no statistically significant difference in the ADC ratio between bpMRI and mpMRI., Conclusions: Diagnostic performance of bpMRI without dynamic contrast enhancement MRI is not significantly different from mpMRI with dynamic contrast enhancement MRI in the detection of csPCa., Competing Interests: The authors declare that there is no relevant or material financial interests that relate to the research described in this paper., (© 2020 Asian Pacific Prostate Society, Published by Elsevier Korea LLC.)

The synergistic effects of a doxorubicin (Dox)-loaded microparticle-microbubble complex (DMMC) and focused ultrasound (FUS) with a short duty cycle (5%) were evaluated in a pancreatic cancer xenograft model established by inoculating immunodeficient mice with CFPAC-1 cells. The efficacy of the DMMC with FUS (study 1), the effect of conjugating the particles as opposed to mixing them (study 2) and the levels of tumor apoptosis and intracellular Dox (study 3) were evaluated. The DMMC with FUS exhibited the lowest tumor growth rate (30.8 mm 3 /wk) and the highest intracellular Dox uptake (8.8%) and tumor cell apoptosis rate (58.7%) among all treatments. DMMC had a significantly lower growth rate than the mixture of Dox-loaded microparticles and microbubbles (44.2 mm 3 /wk, p < 0.01) when they were combined with FUS. In conclusion, DMMC with short-duty-cycle FUS holds promise for tumor growth suppression, which may be attributed to high intracellular Dox uptake., (Copyright © 2020. Published by Elsevier Inc.)

Because chemotherapeutic drugs are often associated with serious side effects, the central topic in modern drug delivery is maximizing the localization of drugs at the target while minimizing non-specific drug interactions at unwanted regions. To address this issue, biocompatible nanoparticles have been developed to enhance the drug half-life while minimizing the associated toxicity. Nevertheless, relying solely on the enhanced half-life and enhanced permeability and retention (EPR) effects has been ineffective, and designing stimulus-sensitive nanoparticles to introduce the precise control of drug release has been desired. In this paper, we introduce a pH-sensitive, reduced albumin nanoparticle in combination with focused ultrasound treatment. Not only did these nanoparticles have superior therapeutic efficacy and toxicity profiles when compared to the free drugs in xenograft mouse models, but we were also able to show that the albumin nanoparticles reported in this paper were more suitable than other types of non-reduced albumin nanoparticles as vehicles for drug delivery. As such, we believe that the albumin nanoparticles presented in this paper with desirable characteristics including the induction of strong anti-tumor response, precise control, and superior safety profiles hold strong potential for preclinical and clinical anticancer therapy.

The purpose of this research is to exploit a weak and semi-supervised deep learning framework to segment prostate cancer in TRUS images, alleviating the time-consuming work of radiologists to draw the boundary of the lesions and training the neural network on the data that do not have complete annotations. A histologic-proven benchmarking dataset of 102 case images was built and 22 images were randomly selected for evaluation. Some portion of the training images were strong supervised, annotated pixel by pixel. Using the strong supervised images, a deep learning neural network was trained. The rest of the training images with only weak supervision, which is just the location of the lesion, were fed to the trained network to produce the intermediate pixelwise labels for the weak supervised images. Then, we retrained the neural network on the all training images with the original labels and the intermediate labels and fed the training images to the retrained network to produce the refined labels. Comparing the distance of the center of mass of the refined labels and the intermediate labels to the weak supervision location, the closer one replaced the previous label, which could be considered as the label updates. After the label updates, test set images were fed to the retrained network for evaluation. The proposed method shows better result with weak and semi-supervised data than the method using only small portion of strong supervised data, although the improvement may not be as much as when the fully strong supervised dataset is used. In terms of mean intersection over union (mIoU), the proposed method reached about 0.6 when the ratio of the strong supervised data was 40%, about 2% decreased performance compared to that of 100% strong supervised case. The proposed method seems to be able to help to alleviate the time-consuming work of radiologists to draw the boundary of the lesions, and to train the neural network on the data that do not have complete annotations.

Recently, combination therapy has received much attention because of its highly therapeutic effect in various types of cancers. In particular, chemo-photodynamic combination therapy has been considered as an outstanding strategy. However, an abnormal increase in tumor angiogenesis caused by reactive oxygen species (ROS) generated during photodynamic therapy (PDT) has been reported. In this study, the complex of doxorubicin (DOX)-encapsulating anti-angiogenic small interfering RNA (siRNA) nanoparticle and chlorin e6 (Ce6)-encapsulating microbubble has been developed to suppress tumor angiogenesis. The first compartment, doxorubicin-encapsulating siRNA nanoparticle, was electrostatically coated using two biocompatible polymers to prevent the damage of genetic materials. The other part, Ce6-encapsulating microbubble, serves as an ultrasound-triggered local delivery system as well as a drug carrier. Both the in vitro and in vivo experimental results demonstrate successful inhibition of angiogenesis with a minimized damage of siRNAs caused by ROS as well as improved therapeutic effect by chemo-photodynamic-gene triple combination therapy using ultrasound-triggered local delivery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate risk factors for bacillus Calmette-Guerin-induced prostatitis in patients with non-muscle invasive bladder cancer following bacillus Calmette-Guerin therapy. Clinical findings from patients with non-muscle invasive bladder cancer who underwent multi-parametric magnetic resonance imaging before transurethral resection of bladder tumor and post-bacillus Calmette-Guerin therapy from March 2004 to August 2018 were evaluated. The population was grouped into patients with or without newly developed lesions on multi-parametric magnetic resonance imaging performed 3 months after bacillus Calmette-Guerin instillation. Patients with prostate-specific antigen levels ≥ 4 ng/mL or prostate cancer were excluded. Univariable and multivariable analyses were performed to determine the predictors of prostate lesions in patients with prior bacillus Calmette-Guerin exposure. Post bacillus Calmette-Guerin-induced prostatitis was found in 50 of the 194 patients (25.8%). No significant differences were observed between the groups except for prostate volumes (33.8 mL vs. 30.8 mL, P = 0.012) and body mass index (25.2 kg/m 2 vs. 24.1 kg/m 2 , P = 0.044). After bacillus Calmette-Guerin exposure, no significant differences in prostate-specific antigen levels, international prostate symptom scores, or post-voiding residual volume were noted. Multivariable regression analysis showed that body mass index (odds ratio, OR = 1.115, P = 0.038) and prostate volume (OR = 3.080, P = 0.012) were significant predictors of post-bacillus Calmette-Guerin prostate lesions. Body mass index and prostate volume may be clinical predictors of prostate lesions after bacillus Calmette-Guerin exposure. Awareness of potential risk factors for this entity should contribute to the clinical decision-making process for patients following bacillus Calmette-Guerin therapy.

Objectives: To evaluate the clinicopathological differences between Prostate Imaging-Reporting and Data System (PI-RADS) version 2 (v2) category 1 and 2 groups. Materials and Methods . We retrospectively reviewed our two institutional clinical databases: (1) transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) fusion biopsy cohort ( n = 706) and (2) radical prostatectomy (RP) cohort ( n = 1403). Subsequently, we performed comparative analyses between PI-RADSv2 category 1 and 2 groups. Clinically significant prostate cancer (csPCa) was defined as the presence of Gleason score (GS) ≥ 3 + 4 in a single biopsy core, and adverse pathology (AP) was defined as high-grade (primary Gleason pattern 4 or any pattern 5) and/or non-organ-confined disease (pT3/N1). We also performed multivariate logistic regression analyses for AP., Results: In the TRUS/MRI fusion biopsy cohort, no significant differences in detection rates of all cancer (18.2% vs. 29.0%, respectively, P = 0.730) or csPCa (9.1% vs. 9.9%, respectively, P = 0.692) were observed between PI-RADSv2 category 1 and 2 groups. There were no significant differences in pathologic outcomes including Gleason score (≥4 + 3, 21.2% vs. 29.9%, respectively, P = 0.420) or detection rate of AP (27.3% vs. 33.8%, respectively, P = 0.561) between the two groups in the RP cohort either. PI-RADSv2 category 1 or 2 had no significant association with AP, even in univariate analysis ( P = 0.299)., Conclusions: PI-RADSv2 categories 1 and 2 had similar performance to predict clinicopathological outcomes. Consequently, these two categories may be unified into a single category. Negative mpMRI does not guarantee the absence of AP, as with csPCa., Competing Interests: All the authors had no conflicts of interest in this study., (Copyright © 2020 Jung Kwon Kim et al.)

We aimed to evaluate the prognostic value of seminal vesicle invasion (SVI) on preoperative multiparametric MRI (mpMRI) in pathological T3b prostate cancer (PCa). We retrospectively reviewed the clinical data of patients who underwent preoperative mpMRI and subsequent radical prostatectomy (RP). A total of 159 patients with pathologic T3b PCa were stratified into two groups based on mpMRI findings (negative vs. positive SVI). A positive SVI was defined as the presence of mpMRI evidence of SVI. In addition, 290 patients with pathologic T3a were also included in this study for further comparative analysis. Fifty-two patients (32.7%) had a positive SVI on preoperative mpMRI. Biochemical recurrence (BCR) occurred in a total of 45 (28.3%) patients, with 25 (23.4%) cases in the negative SVI group and 20 (38.5%) cases in the positive SVI group. Kaplan-Meier survival analysis of the two groups revealed significantly decreased BCR-free survival in the positive SVI group (median, 21 vs. 9 months, log-rank test, P < 0.001). On multivariate Cox regression analysis, pre-biopsy PSA (P = 0.035) and positive SVI on preoperative mpMRI (P = 0.049) were identified as significant predictors of BCR. Upon further comparative analysis with the pathologic T3a group, we also found significant differences among the groups throughout the Kaplan-Meier curve (P < 0.001). Conclusively, the unpredicted (negative) SVI group had a favorable BCR-free survival compared to the positive SVI group. In addition, significant differences were observed in the prognosis of pathologic T3a and these two groups. This suggests that pathologic T3b can be stratified into two categories.

High doses of chemotherapy agents can cause adverse effects. To address this issue, drug-loaded vesicles with minimum drug loss, guided by an external element for precise delivery, are desired. Combinational therapy of both a focused ultrasound-induced drug delivery method and membrane fusogenic liposomes (MFLs) as drug delivery vehicles can satisfy such premises. In this study, we confirmed that the use of a small quantity of docetaxel-loaded membrane fusogenic liposomes (DTX-MFL) with focused ultrasound can induce better antitumor response in a xenograft mouse model compared to conventional docetaxel monotherapy and DTX-MFL only.

Objectives: To validate how established markers of extraprostatic extension (EPE) are applied to anterior prostate cancers (APCs), and to investigate other novel markers if available., Methods: Among 614 histopathologically confirmed APCs from 2011 to 2016, 221 lesions with PiRADS (verion 2) scores ≥ 4 on 3-T multi-parametric MRI were analyzed retrospectively. Two radiologists independently assessed capsular morphology qualitatively with 5-point scale (normal, thinning, bulging, loss, extracapsular disease), and capsule contact length (arc), tumor dimension, and their ratio (arc-dimension ratio) quantitatively. Reproducibility in measurement was assessed with κ and intra-class correlation coefficients (ICCs). Logistic regression analysis was done to find meaningful indicators of EPE. Diagnostic performance of markers was compared to one another with generalized linear model and multi-reader multi-case ROC analysis., Results: Reproducibility was moderate to substantial (κ 0.45-0.73) for qualitative, and moderate to almost perfect (ICC 0.50-0.87) for quantitative features of EPE. Capsular morphology (odds ratio [OR] 1.818), capsule contact length (OR 1.115), tumor dimension (OR 1.035), and arc-dimension ratio (OR 1.846) were independently associated with EPE (p ≤ 0.019). Capsular bulging and capsule contact length of 10 mm as thresholds of EPE demonstrated sensitivity/specificity of 0.58/0.85 and 0.77/0.68, respectively. Capsule contact length yielded greatest AUC (0.784), followed by capsular morphology (0.778), arc-dimension ratio (0.749), and tumor dimension (0.741). Diagnostic performance of capsular morphology, capsule contact length, and arc-dimension ratio was comparable in predicting EPE., Conclusions: Existing markers of EPE applicable regardless of locations of tumors apply similarly to APCs. Arc-dimension ratio may be a novel marker of EPE of APCs., Key Points: • Existing imaging markers of extraprostatic extension (EPE) which have been applied regardless of locations of tumors are reflected similarly to anterior prostate cancers (APCs). • Measuring tumor dimension without capsular assessment may result in insufficient pre-operative prediction of EPE of APCs. • Arc-dimension ratio (capsule contact length divided by tumor dimension) exhibited highest OR and comparable performance to existing features in predicting EPE of APCs.

Purpose: The purpose of this study was to evaluate the ability of contrast-enhanced ultrasonography (CEUS) with microbubbles to detect metastatic lymph nodes (LNs) for treatment planning and prognosis., Methods: For the metastatic LN model, ground VX2 tumor tissues were injected subcutaneously in 12 rabbits, just below the right hind limb. The rabbits were classified into three groups based on the LN area: group A (n=4, >1.9 cm2 ), group B (n=4, 1-1.9 cm2 ), and group C (n=4, <1 cm2 ). The LNs were monitored on CEUS for 10 seconds after injecting 2.5 mL of microbubbles. The percent area of metastatic LNs was calculated on pathologic images and compared with CEUS images., Results: In group A, the mean percent area of metastasis was 40.7%±19.4%. In all cases of metastasis, round-shaped perfusion defects were clearly observed in CEUS images. The metastatic areas were strongly correlated with pathologic findings. The mean percent area in group B was 21.5%±14.4%. The CEUS findings showed multiple nodular perfusion defects, clearly revealing the metastatic areas. In group B, the CEUS and pathologic findings were concordant for three of the four cases. The mean percent area in group C was 9.1%±6.4%. However, in this group, CEUS only detected a small perfusion defect in one case., Conclusion: CEUS has the potential to depict characteristic imaging features of metastatic LNs but still has limitations in early detection.

We aimed to evaluate the effect of 5 alpha-reductase inhibitor (5-ARI) treatment on prostate cancer (PCa) and clinically significant PCa (csPCa) detection in patients undergoing transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) fusion biopsy in the current era of multi-parametric MRI (mpMRI). We retrospectively reviewed our TRUS/MRI fusion biopsy database (n = 706). Eighty (11.3%) patients who had used 5-ARI for more than one year at the time of biopsy were stratified as 5-ARI group. Subsequently, we performed comparative analyses of 5-ARI and non-5-ARI groups. csPCa was defined by a Gleason score ≥3 + 4 in a single biopsy core. Chi-squared test was used to evaluate the performance of mpMRI in predicting PCa/csPCa between the two groups. Multivariate logistic regression analyses were performed to evaluate the significant variables associated with PCa detection. There were no significant differences in PCa/csPCa detection rates between 5-ARI and non-5-ARI groups (all, P > 0.05). In multivariate logistic regression analyses for the evaluation of variables associated with csPCa detection, age (odds ratio [OR], 1.062; 95% confidence interval [CI], 1.035-1.090; P < 0.001), pre-biopsy PSA (OR, 1.062; 95% CI, 1.034-1.090; P < 0.001), prostate volume on TRUS (OR, 0.956; 95% CI, 0.943-0.970, P < 0.001), and PI-RADsV2 category (OR, 5.528; 95% CI, 3.017-10.131; P < 0.001) were found to be significant predictors. However, 5-ARI had no significant association with PCa detection (P = 0.384). Conclusively, 5-ARI therapy did not adversely affect PCa/csPCa detection after TRUS/MRI fusion biopsy, which suggests that exposure to 5-ARI may not impair the performance of mpMRI.

In this research, we exploit an image-based deep learning framework to distinguish three major subtypes of renal cell carcinoma (clear cell, papillary, and chromophobe) using images acquired with computed tomography (CT). A biopsy-proven benchmarking dataset was built from 169 renal cancer cases. In each case, images were acquired at three phases(phase 1, before injection of the contrast agent; phase 2, 1 min after the injection; phase 3, 5 min after the injection). After image acquisition, rectangular ROI (region of interest) in each phase image was marked by radiologists. After cropping the ROIs, a combination weight was multiplied to the three-phase ROI images and the linearly combined images were fed into a deep learning neural network after concatenation. A deep learning neural network was trained to classify the subtypes of renal cell carcinoma, using the drawn ROIs as inputs and the biopsy results as labels. The network showed about 0.85 accuracy, 0.64-0.98 sensitivity, 0.83-0.93 specificity, and 0.9 AUC. The proposed framework which is based on deep learning method and ROIs provided by radiologists showed promising results in renal cell subtype classification. We hope it will help future research on this subject and it can cooperate with radiologists in classifying the subtype of lesion in real clinical situation.

Purpose: To evaluate the characteristics and histological outcomes in patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions undergoing magnetic resonance imaging-guided fusion-targeted biopsy (MRIFTB)., Methods: We retrospectively reviewed 138 patients with PI-RADS category 3 lesions classified using multiparametric MRI who underwent MRIFTB between May 2016 and March 2018. The study population included biopsy-naïve and patients with prior negative biopsy. Univariate and multivariate analyzes were performed to determine significant predictors of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The definition of csPCa was set at Gleason score ≥ 3 + 4., Results: Overall, 114 (82.6%) biopsied lesions were benign and 24 (17.4%) were identified as prostate cancer. Of these 24 lesions, 14 (58.3%) harbored csPCa. Peripheral zone (PZ) lesions were more likely to be associated with malignant disease than transition zone lesions (13.7 vs. 6.2%). Multivariate logistic analysis revealed that age, PZ location, and prostate-specific antigen (PSA) density (P < 0.05) were independent predictors of both PCa and csPCa., Conclusions: A non-negligible number of PI-RADS 3 patients harbor csPCa. Moreover, age, lesion location, and PSA density could be potential clinical predictors of PCa and csPCa. Physicians should be aware of the cancer prevalence of PI-RADS 3 lesions, as the use of the aforementioned factors can help in the decision-making process for these patients.

Background: Crossing the blood-brain barrier (BBB) is crucial for drug delivery to the brain and for treatment of brain tumors, such as glioblastoma, the most common of all primary malignant brain tumors. Microbubble (MB) is oscillated and destroyed by controlling ultrasound (US) parameters. This oscillation and destruction of MB can open the BBB transiently, and a drug can be delivered to the brain. Materials and methods: For testing the efficiency of delivery to the brain, we synthesized a US-sensitizing nanoparticle (NP) complex via chemically binding MBs and NPs for the BBB opening, including near-infrared dye-incorporated albumin nanoparticles (NIR-Alb NPs) for fluorescence detection. Results: The human-derived, biocompatible NIR-Alb NPs did not show significant cytotoxicity to 500 μg/mL for 3 days in four human glioma cell lines. In an in vivo animal study, some US parameters were investigated to determine optimal conditions. The optimized US conditions were applied in a U87MG orthotopic mouse model. We found that the fluorescence intensity in the brain was 1.5 times higher than in the control group. Conclusion: Our US-sensitizing NP complex and US technique could become one of the critical technologies for drug delivery to the brain., Competing Interests: The authors report no conflicts of interest in this work.

Image-guided intra-arterial therapies play a key role in the management of hepatic malignancies. However, limited clinical outcomes suggest the need for new multifunctional drug delivery systems to enhance local drug concentration while reducing systemic adverse reactions. Therefore, we developed the albumin-doxorubicin nanoparticle conjugated microbubble (ADMB) to enhance therapeutic efficiency by sonoporation under exposure to ultrasound. ADMB demonstrated a size distribution of 2.33 ± 1.34 µm and a doxorubicin loading efficiency of 82.7%. The echogenicity of ADMBs was sufficiently generated in the 2-9 MHz frequency range and cavitation depended on the strength of the irradiating ultrasound. In the VX2 rabbit tumor model, ADMB enhanced the therapeutic efficiency under ultrasound exposure, compared to free doxorubicin. The intra-arterial administration of ADMBs sufficiently reduced tumor growth by five times, compared to the control group. Changes in the ADC values and viable tumor fraction supported the fact that the antitumor effect of ADMBs were enhanced by evidence of necrosis ratio (over 70%) and survival tumor cell fraction (20%). Liver toxicity was comparable to that of conventional therapies. In conclusion, this study shows that tumor suppression can be sufficiently maximized by combining ultrasound exposure with intra-arterial ADMB administration., Competing Interests: The authors declare no conflict of interest.

Purpose: We want to investigate whether MR-US fusion can improve the detection rates of clinically significant prostate cancer in patients with prior negative prostate biopsy with PSA level <10 ng/mL., Methods: Thirty nine patients who had previous a history of negative prostate biopsy and PSA levels <10 ng/mL were included in this study. MR was performed before the biopsy and graded using PIRADS V2. We labeled patients with index lesions with PIRADS scores of 3 or above as the MR-positive group, while patients with PIRADS scores of 1 or 2 were the MR-negative group. Two cores of added biopsy (AB) were performed per each index lesion under MR-US fusion. Twelve cores randomized systematic biopsy (SB) were followed. In MR negative group, two cores of AB were obtained in transition zone, followed by SB. Overall cancer and clinically significant cancer detection rates by patients and by cores were analyzed, and compared between MR-positive and negative group., Results: The overall cancer detection rates were 51.3% by patient based and 13.8% by core based. While all of AB positive cancer patients were clinically significant cancer patients, five out of seven (71.4%) AB negative cancer patients were clinically insignificant cancer patients. AB results turned another four cancer patients from insignificant to significant cancer. The cancer detection rates between MR-positive and negative group were statistically significant., Conclusions: Additional biopsy using MR-US fusion showed improved detection of clinically significant prostate cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to compare the diagnostic yield of five systematic randomized protocols using 12-20 biopsy cores with variably-sized phantoms., Methods: A total of 100 prostate phantom models were produced by casting liquid devil's tongue jelly using silicone molds. Sets of 20 phantoms were created with the following volumes: 20 mL, 40 mL, 60 mL, 80 mL, and 100 mL. Three focal lesions were created by injecting 0.5 mL of warm agar solution stained with red, blue, and green ink into each phantom model. The focal lesions were verified by ultrasonography. The systematic randomized biopsy protocols consisted of 12, 14, 16, 18, and 20 biopsy cores. The diagnostic yield of the multiple systematic biopsy protocols was compared., Results: The overall detection rates of each model set were 93.3% for 20 mL, 88.3% for 40 mL, 71.7% for 60 mL, 43.3% for 80 mL, and 30.0% for 100 mL. Statistically significant differences in the detection rate were found between 40 mL and 60 mL and between 60 mL and 80 mL. No statistically significant increase in the detection rate was observed within a given volume set even when the number of core biopsies increased from 12 to 20., Conclusion: The diagnostic yield of systematic randomized biopsies is inversely proportional to the phantom volume.

Background: Interest in an ultrasound-mediated delivery system for effective T 1 -MRI of prostate cancer without adverse effects has steadily increased., Purpose: To develop an ultrasound-responsive dual-modal ultrasound (US)/T 1 -MRI contrast agent for efficient diagnosis of prostate cancer cells overexpressing prostate-specific membrane antigen (PSMA) and assess their potential., Study Type: In vitro., Subjects: Two prostate cancer cell lines., Field Strength/sequence: Each study group underwent 3.0T MRI under a TR 400 msec, TE 10 msec, a 240 × 240 matrix, a flip angle 90°, a slice thickness 3 mm, NSA with 4, bandwidth 115 Hz/pixel, and an FOV of 120 × 120 mm., Assessment: Microscopes, quantitative and qualitative analyzing instruments, and clinical devices were used for assessing this novel contrast agent and its diagnosis effects., Statistical Tests: We used linear regression analyses to determine the longitudinal relaxivity (r 1 ) values of our US/T 1 -MRI contrast agent and gadobutrol., Results: Microbubble+Fe 3+ melanin nanoparticle+peptides (MB+Fe 3+ MNPPs) had a good US contrast effect, like a commercial US agent. The differences of US intensities between them was below 5%. The r 1 values of MB+Fe 3+ MNPPs and gadobutrol were 4.5 and 3.7 s -1 /mM, respectively. More than hundreds of Fe 3+ MNPPs were located in prostate cancer cells treated with MB+Fe 3+ MNPPs and US stimulus, but the number of Fe 3+ MNPPs was below dozens in the other prostate cancer cells expressing less PSMA. The former cells with MB+Fe 3+ MNPPs and US stimulus only showed the highest T 1 -MRI signal because of synergy effects of the peptides targeting the cells and US stimulus for delivery of Fe 3+ MNPPs to the cells. No cytotoxicity of MB+Fe 3+ MNPPs was confirmed by using a WST assay. Viability of the cells with the complexes was above 90%., Data Conclusion: We synthesized MB+Fe 3+ MNPPs as a potential US/T 1 -MRI contrast agent. This complex was applicable for diagnosing desired prostate cancer cells., Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1610-1616., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: We analyzed the data of consecutive patients who had preoperative multiparametric magnetic resonance imaging (mpMRI) and underwent radical prostatectomy (RP) to evaluate the actual performance of mpMRI among biopsy-proven prostate cancer (PCa) patients in predicting favorable pathology in the real-life clinical setting., Methods: Among a total 730 biopsy-proven PCa patients underwent RP, the preoperative mpMRIs of 534 patients were positive, demonstrating one or more PI-RADs V2 grade ≥ 2 lesion(s). Other 196 mpMRIs were classified as negative, without any suspicious lesion. Pathology was classified to be unfavorable when showing Gleason score (GS) 4/5 or pT3/N1 features. Significant cancer was defined as non-organ-confined, GS 4/5, or cancer volume of ≥ 0.5 mL., Results: Among a total 196 negative preoperative mpMRI patients, final RP pathology showed that 20 (10.2%) had pT3 disease and 2 (1.0%) had pN1 disease. Regarding the pathologic Gleason score, 117 (59.7%) had GS 3 + 4 and 44 (22.4%) had GS ≥ 4 + 3. The rate of a favorable PCa and an insignificant cancer was as low as 14.3% and 10.2%. Even among only the 101 D'Amico low-risk patients with negative MRI, the rates of a favorable pathology and an insignificant cancer were only 18.2% and 12.7%. The sensitivity, specificity, positive, and negative predictive value of mpMRI to predict a significant cancer were 74.3%, 45.5%, 95.5%, and 10.2%, respectively., Conclusions: In the real-life clinical setting, mpMRI demonstrated limited performance in the prediction of favorable and insignificant prostate cancer as a negative mpMRI could not guarantee the absence of unfavorable pathology among PCa patients.

Background: To evaluate the effectiveness of an antibiotic regimen for prostate biopsy by analyzing patients who were hospitalized because of complications after transrectal ultrasound-guided prostate biopsy., Methods: We reviewed retrospectively the medical records of 10,339 patients who underwent transrectal ultrasound-guided prostate biopsy at our institution from May 2003 to April 2017. We excluded patients with low quality data. All patients underwent urine culture before transrectal ultrasound-guided prostate biopsy and received intravenous antibiotic agents 30-60 minutes before biopsy. Patients were either given prophylactic quinolone or cephalosporin (second or third generation). Clinicopathologic factors including patient age, antibiotic regimen, number of biopsy cores, body mass index, prostate specific antigen, prostate volume, and infection-related complications that required hospitalization were subsequently analyzed., Results: A total of 9,487 patients were included in the final analysis, of whom 33 patients (0.35%) were hospitalized because of infection-related complications. Infection-related hospitalization rates were lower in patients who received cephalosporin (0.2%) than in patients who received quinolone (1.59%). At our institution, cephalosporin has been used predominantly to prevent post-biopsy infections since February 2013. Only five patients (0.12%) developed infection-related complications of the 3,863 patient who underwent transrectal ultrasound-guided prostate biopsy since February 2013. Multivariable analysis revealed that use of second- or third-generation cephalosporin was the only independent predictor of infection-related complications., Conclusion: Implementing an effective antibiotic prophylaxis regimen at our institution by using second- or third-generation cephalosporin could reduce infection-related complications after transrectal ultrasound-guided prostate biopsy.

The use of gamification in healthcare has been gaining popularity. This prospective, randomized, clinical trial was designed to evaluate whether gamification of the preoperative process-via virtual reality (VR) gaming that provides a vivid, immersive and realistic experience-could reduce preoperative anxiety in children. Seventy children scheduled for elective surgery under general anesthesia were randomly divided into either the control or gamification group. Children in the control group received conventional education regarding the preoperative process, whereas those in the gamification group played a 5 min VR game experiencing the preoperative experience. Preoperative anxiety, induction compliance checklist (ICC), and procedural behavior rating scale (PBRS) were measured. Sixty-nine children were included in the final analysis (control group = 35, gamification = 34). Preoperative anxiety (28.3 [23.3⁻36.7] vs. 46.7 [31.7⁻51.7]; p < 0.001) and intraoperative compliance measured using ICC ( p = 0.038) were lower in the gamification group than in the control group. However, PBRS ( p = 0.092) and parent/guardian satisfaction ( p = 0.268) were comparable between the two groups. VR experience of the preoperative process could reduce preoperative anxiety and improve compliance during anesthetic induction in children undergoing elective surgery and general anesthesia.

Background: Three-dimensional (3D) printing has been introduced as a novel technique to produce 3D objects. We tried to evaluate the clinical usefulness of 3D-printed renal model in performing partial nephrectomy (PN) and also in the education of medical students., Materials and Methods: We prospectively produced personalized renal models using 3D-printing methods from preoperative computed tomography (CT) images in a total of 10 patients. Two different groups (urologist and student group) appraised the clinical usefulness of 3D-renal models by answering questionnaires., Results: After application of 3D renal models, the urologist group gave highly positive responses in asking clinical usefulness of 3D-model among PN (understanding personal anatomy: 8.9 / 10, preoperative surgical planning: 8.2 / 10, intraoperative tumor localization: 8.4 / 10, plan for further utilization in future: 8.3 / 10, clinical usefulness in complete endophytic mass: 9.5 / 10). The student group located each renal tumor correctly in 47.3% when they solely interpreted the CT images. After the introduction of 3D-models, the rate of correct answers was significantly elevated to 70.0% (p < 0.001). The subjective difficulty level in localizing renal tumor was also significantly low (52% versus 27%, p < 0.001) when they utilized 3D-models., Conclusion: The personalized 3D renal model was revealed to significantly enhance the understanding of correct renal anatomy in patients with renal tumors in both urologist and student groups. These models can be useful for establishing the perioperative planning and also education program for medical students., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objectives: Diffusion-weighted imaging (DWI) has been shown to be an important component of multiparametric magnetic resonance imaging (mpMRI). We compared performance of DWI for detection of prostate cancer (PCa) in peripheral zone (PZ) and transition zone (TZ) of prostate., Materials and Methods: We reviewed data of 460 subjects who underwent preoperative 3.0-Tesla mpMRI and subsequently radical prostatectomy. Level of suspicion for PCa was graded using 5-grade Likert-scale from DWI. Topographic analyses were performed for location of tumor foci at each surgical specimen. Among those with DWI grade ≥ III, we analyzed concordance rate on the location of radiologic and pathologic index lesions between DWI and surgical specimens., Results: Among 460 patients, 351 (76.3%) patients showed suspicious DWI lesions (57.5% in PZ, 42.5% in TZ). Multivariates regression analyses revealed significant associations between high DWI grade and adverse pathologic outcomes including pathologic stage, Gleason score, tumor volume and extracapsular extension (all p < 0.05). Overall concordance rates between DWI and surgical specimen were 75.8%, significantly higher in PZ than TZ (82.2% vs. 67.1% p = 0.002). Such concordance rate showed a positive linear association with increase in DWI grading (p < 0.001). Among 109 patients with DWI grade I-II, 28 (25.7%) harbored high grade disease (pathologic Gleason score ≥ 4 + 3)., Conclusions: DWI detects tumors in PZ of prostate more accurately than those in TZ. Such accuracy of DWI was shown to be more evident with higher DWI grade. Meanwhile, a negative DWI did not guarantee absence of high grade PCa., Competing Interests: The authors have declared that no competing interests exist.

Although the causes of hypertension are usually unknown, about 10% of the cases occur secondary to specific etiologies, which are often treatable. Common categories of secondary hypertension include renal parenchymal disease, renovascular stenosis, vascular and endocrinologic disorders. For diseases involving the renal parenchyma and adrenal glands, ultrasonography (US), computed tomography (CT) or magnetic resonance (MR) imaging is recommended. For renovascular stenosis and vascular disorders, Doppler US, conventional or noninvasive (CT or MR) angiography is an appropriate modality. Nuclear imaging can be useful in the differential diagnosis of endocrine causes. Radiologists should understand the role of each imaging modality and its typical findings in various causes of secondary hypertension. This article focuses on appropriate imaging approaches in accordance with the categorized etiologies leading to hypertension.