[Show abstract][Hide abstract] ABSTRACT: Approximately 15% of patients who undergo radical prostatectomy (RP) for prostate cancer develop local recurrence, which is heralded by a rise in serum prostate-specific antigen (PSA) levels. Early detection and treatment of recurrence improves the outcome of salvage treatment. We investigated the ability of multiparametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) fusion-guided biopsy (FGB) combined with "cognitive biopsy" to confirm local recurrence of prostate cancer after RP.
In this retrospective study conducted between January 2010 and December 2014, patients with rising PSA levels after RP who had no known evidence of distant metastases underwent mpMRI including T2-weighted (T2W) imaging, diffusion-weighted imaging, dynamic contrast-enhanced (DCE) MRI at 3 Tesla, and subsequent MRI-ultrasound fusion biopsy with cognitive assistance. The detection rate of locally recurrent disease was determined.
A total of 10 patients (mean age = 67y, mean PSA level = 3.44ng/ml) met the inclusion criteria. Of the 10 patients, all had positive findings suspicious for local recurrence on mpMRI per entrance criterion. The most important features on mpMRI were early enhancement on DCE MR images and hypointensity on T2W images. The average lesion diameter on mpMRI was 1.12cm (range: 0.40-2.20cm). All suspicious lesions (16/16, 100%) were positive on T2W MR images, 14 (89%) showed positive features on apparent diffusion coefficient maps of diffusion-weighted images, and 16 (100%) were positive on DCE MR images. MRI-TRUS FGBs were positive in 10/16 lesions (62.5%) and 8/10 (80%) patients.
MRI-TRUS FGB with cognitive assistance is able to detect and diagnose locally recurrent lesions after RP, even at low PSA levels. This may facilitate early detection of recurrent disease and improve salvage treatment outcomes.
Published by Elsevier Inc.
[Show abstract][Hide abstract] ABSTRACT: (18)F-FDG PET/CT is used to characterize many malignancies, but is not recommended for localized prostate cancer. This study explores the value of multi-parametric MRI (mpMRI) in characterizing incidental prostate (18)F-FDG uptake.
Thirty-one patients who underwent (18)F-FDG PET/CT for reasons unrelated to prostate cancer and prostate mpMRI were eligible for this retrospective study. The mpMRI included T2-weighted (T2W), dynamic contrast enhancement (DCE), apparent diffusion coefficient (ADC), and MR spectroscopy (MRS) sequences. Fourteen patients were excluded (n = 8 insufficient histopathology, n = 6 radical prostatectomy before PET), and final analysis included 17 patients. A nuclear medicine physician, blinded to clinicopathologic findings, identified suspicious areas and maximum standardized uptake values (SUVmax) on (18)F-FDG PET/CT. Sector-based imaging findings were correlated with annotated histopathology from whole-mount or MRI/transrectal ultrasound fusion biopsy samples. Positive predictive values (PPVs) were estimated using generalized estimating equations with logit link. Results were evaluated with Kruskal-Wallis and Dunn's multiple comparisons tests.
The PPV of (18)F-FDG PET alone in detecting prostate cancer was 0.65. Combining (18)F-FDG PET as a base parameter with mpMRI (T2W, DCE, ADC, and MRS) increased the PPV to 0.82, 0.83, 0.83, and 0.94, respectively. All benign lesions had SUVmax < 6. Malignant lesions had higher SUVmax values that correlated with Gleason scores. There was a significant difference in SUVmax per prostate between the Gleason ≥ 4 + 5 and benign categories (p = 0.03).
Focal incidental prostate (18)F-FDG uptake has low clinical utility alone, but regions of uptake may harbor high-grade prostate cancer, especially if SUVmax > 6. Using mpMRI to further evaluate incidental (18)F-FDG uptake aids the diagnosis of prostate cancer.
[Show abstract][Hide abstract] ABSTRACT: The imaging features of unresectable hepatic malignancies in patients who underwent radiofrequency ablation (RFA) in combination with lyso-thermosensitive liposomal doxorubicin (LTLD) were determined.
A phase I dose escalation study combining RFA with LTLD was performed with peri- and post- procedural CT and MRI. Imaging features were analyzed and measured in terms of ablative zone size and surrounding penumbra size. The dynamic imaging appearance was described qualitatively immediately following the procedure and at 1-month follow-up. The control group receiving liver RFA without LTLD was compared to the study group in terms of imaging features and post-ablative zone size dynamics at follow-up.
Post-treatment scans of hepatic lesions treated with RFA and LTLD have distinctive imaging characteristics when compared to those treated with RFA alone. The addition of LTLD resulted in a regular or smooth enhancing rim on T1W MRI which often correlated with increased attenuation on CT. The LTLD-treated ablation zones were stable or enlarged at follow-up four weeks later in 69 % of study subjects as opposed to conventional RFA where the ablation zone underwent involution compared to imaging acquired immediately after the procedure.
The imaging features following RFA with LTLD were different from those after standard RFA and can mimic residual or recurrent tumor. Knowledge of the subtle findings between the two groups can help avoid misinterpretation and proper identification of treatment failure in this setting. Increased size of the LTLD-treated ablation zone after RFA suggests the ongoing drug-induced biological effects.
CardioVascular and Interventional Radiology 07/2015; DOI:10.1007/s00270-015-1186-0 · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Novel approaches allowing efficient, readily translatable image-guided drug delivery (IGDD) against solid tumours is needed. The objectives of this study were to: 1) develop echogenic low temperature sensitive liposomes (E-LTSLs) loaded with an ultrasound (US) contrast agent (perfluoropentane, PFP), 2) determine the in vitro and in vivo stability of contrast agent encapsulation, 3) co-encapsulate and characterise doxorubicin (Dox) E-LTSL, and cellular uptake and cytotoxicity in combination with high intensity focused ultrasound (HIFU).
E-LTSLs were loaded passively with PFP and actively with Dox. PFP encapsulation in E-LTSL was determined by transmission electron microscopy (TEM), and US imageability was determined in tissue-mimicking phantoms and mouse tumour model. Dox release from E-LTSL in physiological buffer was quantified by fluorescence spectroscopy. Cellular uptake and cytotoxicity of E-LTSL in the presence of HIFU-induced mild hyperthermia (∼40-42 °C) was determined in a 3D tumour spheroid model.
TEM and US confirmed that the PFP emulsion was contained within LTSLs. Phantom and animal studies showed that the E-LTSLs were echogenic. Temperature versus size increase and Dox release kinetics of E-LTSLs demonstrated no difference compared to LTSL alone. Dox release was <5% within 1 h at baseline (25 °C) and body (37 °C) temperatures, and was >99% under hyperthermia. E-LTSL plus HIFU achieved significantly greater Dox uptake in spheroids and cytotoxicity compared to body temperature.
A stable US-imageable liposome co-loaded with Dox and PFP for in vivo IGDD was developed. Data suggest that HIFU can induce cellular uptake and toxicity with E-LTSLs.
International Journal of Hyperthermia 07/2015; DOI:10.3109/02656736.2015.1057622 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Therapeutic embolization of blood vessels is a minimally invasive, catheter-based procedure performed with solid or liquid emboli to treat bleeding, vascular malformations, and vascular tumors. Hepatocellular carcinoma (HCC) affects about half a million people per year. When unresectable, HCC is treated with embolization and local drug therapy by transarterial chemoembolization (TACE). For TACE, drug eluting beads (DC Bead(®)) may be used to occlude or reduce arterial blood supply and deliver chemotherapeutics locally to the tumor. Although this treatment has been shown to be safe and to improve patient survival, the procedure lacks imaging feedback regarding the location of embolic agent and drug coverage. To address this shortcoming, herein we report the synthesis and characterization of image-able drug eluting beads (iBeads) from the commercial DC Bead(®) product. Two different radiopaque beads were synthesized. In one approach, embolic beads were conjugated with 2,3,5-triiodobenzyl alcohol in the presence of 1,1'-carbonyldiimidazol to give iBead I. iBead II was synthesized with a similar approach but instead using a trimethylenediamine spacer and 2,3,5-triiodobenzoic acid. Doxorubicin was loaded into the iBeads II using a previously reported method. Size and shape of iBeads were evaluated using an upright microscope and their conspicuity assessed using a clinical CT and micro-CT. Bland and Dox-loaded iBeads II visualized with both clinical CT and microCT. Under microCT, individual bland and Dox loaded beads had a mean attenuation of 7904 ± 804 and 11,873.96 ± 706.12 HU, respectively. These iBeads have the potential to enhance image-guided TACE procedures by providing localization of embolic-particle and drug.
Journal of Materials Science Materials in Medicine 06/2015; 26(6):5530. DOI:10.1007/s10856-015-5530-3 · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Local binary pattern (LBP) is a simple gray scale descriptor to characterize the local distribution of the gray levels in an image. Multi-resolution LBP and/or combinations of the LBPs have shown to be effective in texture image analysis. However, it is unclear what resolutions or combinations to choose for texture analysis. Examining all the possible cases is impractical and intractable due to the exponential growth in a feature space. This limits the accuracy and time- and space-efficiency of LBP. Here, we propose a data mining approach for LBP, which efficiently explores a high-dimensional feature space and finds a relatively smaller number of discriminative features. The features can be any combinations of LBPs. These may not be achievable with conventional approaches. Hence, our approach not only fully utilizes the capability of LBP but also maintains the low computational complexity. We incorporated three different descriptors (LBP, local contrast measure, and local directional derivative measure) with three spatial resolutions and evaluated our approach using two comprehensive texture databases. The results demonstrated the effectiveness and robustness of our approach to different experimental designs and texture images.
Expert Systems with Applications 06/2015; 42(9):4529-4539. DOI:10.1016/j.eswa.2015.01.055 · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The posterior subcapsular region of the prostate is often undersampled by transrectal ultrasound (TRUS)-guided biopsy. The close proximity of these lesions to the posterior capsular wall of the prostate makes them difficult to localize while increasing the need for early detection because of their increased risk for extracapsular extension. We retrospectively evaluated the multiparametric MRI (mpMRI) features of subcapsular prostate cancers to make radiologists more aware of this condition.
Between January 2010 and July 2014, all patients referred for 3T mpMRI and subsequent MR-US Fusion-guided biopsy (FgBx) and systematic 12-core sextant biopsy (SBx) under an IRB approved protocol, were reviewed, and imaging confirmed subcapsular prostate cancers were identified. Subcapsular lesions were defined as thin lesions that were just inside the prostate capsule. Matching patient demographics and clinical findings including age, PSA, PSA density, whole prostate volume, history of prostate cancer, Gleason score, and clinical management were tabulated.
Of 992 eligible patients, 33 patients had subcapsular lesions in the prostate detected by mpMRI. Mean age, PSA, and prostate volume in this group were 63 years (range: 52-76 years), 8.4 ng/mL (range: 1.22-65.20), and 53 mL (range: 12-125 mL), respectively. The combination biopsy (SBx + FgBx) confirmed prostate cancer in 24 of 33 patients (72.7%) and in 9 patients the biopsy was negative. Of the 24 cancers, 19 were confirmed on both FgBx and conventional biopsy; however, 5 cancers were only detected on FgBx. In 4 of the 19 patients in which both biopsy methods were positive, the FgBx yielded a higher Gleason score.
Subcapsular lesions on mpMRI are relatively infrequent but are usually malignant. Although the majority are confirmed on conventional 12-core biopsies, about 20% of these lesions require FgBx for diagnosis, and FgBx more accurately grades the lesions in another 20%. Thus, FgBx is of considerable benefit in confirming the diagnosis of subcapsular prostate cancer despite their proximity to the prostatic capsule.
[Show abstract][Hide abstract] ABSTRACT: To correlate the highest percentage core involvement (HPCI) and corresponding tumor length (CTL), on systematic 12-core biopsy (SBx) and targeted magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion biopsy (TBx), with total MRI prostate cancer (PCa) tumor volume (TV).
Fifty patients meeting criteria for active surveillance (AS) based on outside SBx, who underwent 3.0T multiparametric prostate MRI (MP-MRI), followed by SBx and TBx during the same session at our institution were examined. PCa TV's were calculated using MP-MRI and then correlated using bivariate analysis with the HPCI and CTL, for SBx and TBx.
For TBx, HPCI and CTL showed a positive correlation (R2 = 0.31, p<0.0001 and R2 = 0.37, p<0.0001 respectively) with total MRI PCa TV, whereas for SBx these parameters showed a poor correlation (R2 = 0.00006, p=0.96 and R2 = 0.0004, p=0.89 respectively). For detection of patients with clinically significant MRI derived tumor burden greater than 500 mm3, SBx was 25% sensitive, 90.9% specific (falsely elevated due to missed tumors and extremely low sensitivity) and 54% accurate in comparison to TBx, which was 53.6% sensitive, 86.4% specific and 68% accurate.
HPCI and CTL on TBx positively correlates with total MRI PCa TV, whereas there was no correlation seen with SBx. TBx is superior to SBx for detecting tumor burden greater than 500 mm3. When using biopsy positive MRI derived TV's, TBx better reflects overall disease burden, improving risk stratification amongst candidates for active surveillance.
Journal of endourology / Endourological Society 04/2015; DOI:10.1089/end.2015.0027 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The authors propose a computer-aided diagnosis (CAD) system for prostate cancer to aid in improving the accuracy, reproducibility, and standardization of multiparametric magnetic resonance imaging (MRI).
The proposed system utilizes two MRI sequences [T2-weighted MRI and high-b-value (b = 2000 s/mm2) diffusion-weighted imaging (DWI)] and texture features based on local binary patterns. A three-stage feature selection method is employed to provide the most discriminative features. The authors included a total of 244 patients. Training the CAD system on 108 patients (78 MR-positive prostate cancers and 105 benign MR-positive lesions), two validation studies were retrospectively performed on 136 patients (68 MR-positive prostate cancers, 111 benign MR-positive lesions, and 117 MR-negative benign lesions).
In distinguishing cancer from MR-positive benign lesions, an area under receiver operating characteristic curve (AUC) of 0.83 [95% confidence interval (CI): 0.76–0.89] was achieved. For cancer vs MR-positive or MR-negative benign lesions, the authors obtained an AUC of 0.89 AUC (95% CI: 0.84–0.93). The performance of the CAD system was not dependent on the specific regions of the prostate, e.g., a peripheral zone or transition zone. Moreover, the CAD system outperformed other combinations of MRI sequences: T2W MRI, high-b-value DWI, and the standard apparent diffusion coefficient (ADC) map of DWI.
The novel CAD system is able to detect the discriminative texture features for cancer detection and localization and is a promising tool for improving the quality and efficiency of prostate cancer diagnosis.
Medical Physics 04/2015; 42(5):2368-2378. DOI:10.1118/1.4918318 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent years, fusion of multi-parametric MRI (mp-MRI) with transrectal ultrasound (TRUS)-guided biopsy has enabled targeted prostate biopsy with improved cancer yield. Target identification is solely based on information from mp-MRI, which is subsequently transferred to the subject coordinates through an image registration approach. mp-MRI has shown to be highly sensitive to detect higher-grade prostate cancer, but suffers from a high rate of false positives for lower-grade cancer, leading to unnecessary biopsies. This paper utilizes a machine-learning framework to further improve the sensitivity of targeted biopsy through analyzing temporal ultrasound data backscattered from the prostate tissue.
Temporal ultrasound data were acquired during targeted fusion prostate biopsy from suspicious cancer foci identified in mp-MRI. Several spectral features, representing the signature of backscattered signal from the tissue, were extracted from the temporal ultrasound data. A supervised support vector machine classification model was trained to relate the features to the result of histopathology analysis of biopsy cores obtained from cancer foci. The model was used to predict the label of biopsy cores for mp-MRI-identified targets in an independent group of subjects.
Training of the classier was performed on data obtained from 35 biopsy cores. A fivefold cross-validation strategy was utilized to examine the consistency of the selected features from temporal ultrasound data, where we achieved the classification accuracy and area under receiver operating characteristic curve of 94 % and 0.98, respectively. Subsequently, an independent group of 25 biopsy cores was used for validation of the model, in which mp-MRI had identified suspicious cancer foci. Using the trained model, we predicted the tissue pathology using temporal ultrasound data: 16 out of 17 benign cores, as well as all three higher-grade cancer cores, were correctly identified.
The results show that temporal analysis of ultrasound data is potentially an effective approach to complement mp-MRI-TRUS-guided prostate cancer biopsy, specially to reduce the number of unnecessary biopsies and to reliably identify higher-grade cancers.
International Journal of Computer Assisted Radiology and Surgery 04/2015; 10(6). DOI:10.1007/s11548-015-1184-3 · 1.66 Impact Factor