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  • 1
    Keywords: CANCER ; tumor ; MODEL ; THERAPY ; DIAGNOSIS ; MRI ; magnetic resonance imaging ; PERFORMANCE ; EXPERIENCE ; prostate cancer ; FUSION ; BIOPSY ; GUIDANCE ; three-dimensional imaging ; GUIDED BIOPSY ; MAPPING BIOPSY ; TRUS
    Abstract: Background. A key challenge for prostate cancer (PC) therapy is to exactly diagnose tumor lesions. In this context we describe a new stereotactic prostate biopsy system, which integrates pre-interventional MRI with peri-interventional ultrasound for targeted perineal prostate biopsies. Furthermore, the novel system allows exact documentation of biopsies in three dimensions. Patients and methods. Stereotactic biopsy was performed in 50 consecutive men with suspicion of PC [median age 67 years (42-77), mean PSA 8.9 +/- 6.8 ng/ml, and mean prostate volume 51 +/- 23.7 ml]. Twenty-five of these patients (50%) had already had a negative transrectal ultrasound (TRUS)-guided biopsy. All men underwent multiparametric, contrast-enhanced 3T MRI without endorectal coil. Suspicious lesions were marked before the obtained data were transferred to a novel stereotactic biopsy system. Using a custom-made biplane TRUS probe mounted on a stepper, 3-D ultrasound data were generated and fused with the MRI. As a result, suspicious MRI lesions were superimposed onto the TRUS data. Next, 3-D biopsy planning was performed including systematic biopsies from the peripheral zone of the prostate. According to local standards patients were treated with perioperative quinolone antibiotics and applied a rectal enema the evening before the procedure. Perineal biopsies were taken under live US imaging, and the location of each biopsy was documented in an individual 3-D model. Feasibility, safety, target registration error, and cancer detection were evaluated. Results. The median number of biopsies taken per patient was 24 (12-36). In 27 men of the initial cohort of 50 consecutive patients presented here, biopsy samples showed PC (54%). In patients undergoing their first biopsy, cancerous lesions were diagnosed in 13 of 19 patients (68%). The result was positive in 36% of men undergoing a re-biopsy without previous cancer diagnosis (9/25). A positive correlation between MRI findings and histopathology was found in 72%. In MRI lesions marked as highly suspicious, the tumor detection rate was 100% (13/13). Looking at single cores from highly suspicious lesions, 40 of 75 (53%) biopsies were positive. The target registration error of the first 1,159 biopsy cores was 1.7 mm. Regarding adverse effects, one patient experienced urinary retention and one patient a perineal hematoma. Urinary tract infections did not occur. Conclusion. Perineal stereotactic prostate biopsies guided by the combination of MRI and ultrasound allow effective examination of suspicious MRI lesions. Each biopsy core taken is documented accurately for its location in 3-D enabling MRI validation and tailored treatment planning. The morbidity of the procedure was minimal
    Type of Publication: Journal article published
    PubMed ID: 21935634
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  • 2
    Abstract: PURPOSE: Laparoscopic interventions require the precise navigation of medical instruments through the patient's body, while taking critical structures into account. Although numerous concepts have been proposed for displaying subsurface anatomical detail using augmented reality, clinical translation of these methods has suffered from a lack of robustness as well as from cumbersome integration into the clinical workflow. The purpose of this study was to investigate the feasibility of a new approach to intra-operative registration based on fluorescent markers. METHODS: The proposed approach to augmented reality visualization relies on metabolizable fluorescent markers that are attached to the target organ to guide a 2D/3D intra-operative registration algorithm. In an ex vivo porcine study, marker tracking performance is evaluated in the presence of smoke, blood, and tissue in the field of view of the endoscope. RESULTS: In contrast to state-of-the-art needle-shaped fiducial markers, the fluorescent markers can be reliably tracked when occluded by smoke, blood or tissue. This makes the new 2D/3D intra-operative registration approach considerably more robust than state-of-the-art marker-based methods. CONCLUSION: As the concept can be smoothly integrated into the clinical workflow, its potential for application in clinical laparoscopy is high.
    Type of Publication: Journal article published
    PubMed ID: 27177759
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  • 3
    Keywords: MODEL ; PROSTATE ; IMAGES ; TRIALS ; REGISTRATION ; HEAD ; GUIDANCE ; navigation ; REAL ; TRANSRECTAL ULTRASOUND GUIDANCE
    Abstract: PURPOSE: We present an augmented reality (AR) navigation system that conveys virtual organ models generated from transrectal ultrasonography (TRUS) onto a real laparoscopic video during radical prostatectomy. By providing this additional information about the actual anatomy, we can support surgeons in their working decisions. This work reports the system's first in-vivo application. MATERIALS AND METHODS: The system uses custom-developed needles with colored heads that are inserted into the prostate as soon as the organ surface is uncovered. These navigation aids are once segmented in three-dimensional (3D) TRUS data that is acquired right after the placement of the needles and then continuously tracked in the laparoscopic video images by the surgical navigation system. The navigation system traces the navigation aids in real time and computes a registration between TRUS image and laparoscopic video based on the two-dimensional-three dimensional (2D-3D) point correspondences. With this registration, the system correctly superimposes TRUS-based 3D information on an additional AR monitor placed next to the normal laparoscopic screen. Surgical navigation guidance took place until the prostate was removed from the rectal wall. Finally, the navigation aids were removed together with the specimen inside the specimen bag. RESULTS: The initial human in-vivo application of the surgical navigation system was successful. No complications occurred, the prostate was removed together with the navigation aids, and the system supported the surgeons as intended with an AR visualization in real time. In case of tissue deformations, changes in the spatial configuration of the navigation aids are detected, which preserves the system from erroneous navigation visualization. CONCLUSIONS: Feasibility of the navigation system was shown in the first in-vivo application. TRUS information could be superimposed via AR in real time. To show the benefit for the patient, results obtained from a larger number of trials are needed.
    Type of Publication: Journal article published
    PubMed ID: 21970336
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  • 4
    Abstract: Resection of tumors using targeted dual-modality probes combining preoperative imaging with intraoperative guidance is of high clinical relevance and might considerably affect the outcome of prostate cancer therapy. This work aimed at the development of dual-labeled prostate-specific membrane antigen (PSMA) inhibitors derived from the established N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC)-based PET tracer (68)Ga-Glu-urea-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-11) to allow accurate intraoperative detection of PSMA-positive tumors. Methods: A series of novel PSMA-targeting fluorescent dye conjugates of Glu-urea-Lys-HBED-CC was synthesized, and their biologic properties were determined in cell-based assays and confocal microscopy. As a preclinical proof of concept, specific tumor uptake, pharmacokinetics, and feasibility for intraoperative fluorescence guidance were investigated in tumor-bearing mice and healthy pigs. Results: The designed dual-labeled PSMA inhibitors exhibited high binding affinity and PSMA-specific effective internalization. Conjugation of fluorescein isothiocyanate (10.86 +/- 0.94 percentage injected dose [%ID]/g), IRDye800CW (13.66 +/- 3.73 %ID/g), and DyLight800 (15.62 +/- 5.52 %ID/g) resulted in a significantly increased specific tumor uptake, whereas (68)Ga-Glu-urea-Lys-HBED-CC-AlexaFluor488 (9.12 +/- 5.47 %ID/g) revealed a tumor uptake similar to that of (68)Ga-PSMA-11 (4.89 +/- 1.34 %ID/g). The first proof-of-concept studies with the clinically relevant candidate (68)Ga-Glu-urea-Lys-HBED-CC-IRDye800CW reinforced a fast, specific enrichment in PSMA-positive tumors, with rapid background clearance. With regard to intraoperative navigation, a specific fluorescence signal was detected in PSMA-expressing tissue. Conclusion: This study demonstrated that PSMA-11-derived dual-labeled dye conjugates are feasible for providing PSMA-specific pre-, intra-, and postoperative detection of prostate cancer lesions and have high potential for future clinical translation.
    Type of Publication: Journal article published
    PubMed ID: 29191856
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  • 5
    Publication Date: 2018-04-03
    Description: Resection of tumors using targeted dual-modality probes combining preoperative imaging with intraoperative guidance is of high clinical relevance and might considerably affect the outcome of prostate cancer therapy. This work aimed at the development of dual-labeled prostate-specific membrane antigen (PSMA) inhibitors derived from the established N,N' -bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine- N,N' -diacetic acid (HBED-CC)–based PET tracer 68 Ga-Glu-urea-Lys(Ahx)-HBED-CC ( 68 Ga-PSMA-11) to allow accurate intraoperative detection of PSMA-positive tumors. Methods: A series of novel PSMA-targeting fluorescent dye conjugates of Glu-urea-Lys-HBED-CC was synthesized, and their biologic properties were determined in cell-based assays and confocal microscopy. As a preclinical proof of concept, specific tumor uptake, pharmacokinetics, and feasibility for intraoperative fluorescence guidance were investigated in tumor-bearing mice and healthy pigs. Results: The designed dual-labeled PSMA inhibitors exhibited high binding affinity and PSMA-specific effective internalization. Conjugation of fluorescein isothiocyanate (10.86 ± 0.94 percentage injected dose [%ID]/g), IRDye800CW (13.66 ± 3.73 %ID/g), and DyLight800 (15.62 ± 5.52 %ID/g) resulted in a significantly increased specific tumor uptake, whereas 68 Ga-Glu-urea-Lys-HBED-CC-AlexaFluor488 (9.12 ± 5.47 %ID/g) revealed a tumor uptake similar to that of 68 Ga-PSMA-11 (4.89 ± 1.34 %ID/g). The first proof-of-concept studies with the clinically relevant candidate 68 Ga-Glu-urea-Lys-HBED-CC-IRDye800CW reinforced a fast, specific enrichment in PSMA-positive tumors, with rapid background clearance. With regard to intraoperative navigation, a specific fluorescence signal was detected in PSMA-expressing tissue. Conclusion: This study demonstrated that PSMA-11–derived dual-labeled dye conjugates are feasible for providing PSMA-specific pre-, intra-, and postoperative detection of prostate cancer lesions and have high potential for future clinical translation.
    Print ISSN: 0022-3123
    Topics: Medicine
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