4D perfusion CT of prostate cancer for image-guided radiotherapy planning: A proof of concept study.

PURPOSE: Advanced forms of prostate cancer (PCa) radiotherapy with either external beam therapy or brachytherapy delivery techniques aim for a focal boost and thus require accurate lesion localization and lesion segmentation for subsequent treatment planning. This study prospectively evaluated dynamic contrast-enhanced computed tomography (DCE-CT) for the detection of prostate cancer lesions in the peripheral zone (PZ) using qualitative and quantitative image analysis compared to multiparametric magnet resonance imaging (mpMRI) of the prostate. METHODS: With local ethics committee approval, 14 patients (mean age, 67 years; range, 57-78 years; PSA, mean 8.1 ng/ml; range, 3.5-26.0) underwent DCE-CT, as well as mpMRI of the prostate, including standard T2, diffusion-weighted imaging (DWI), and DCE-MRI sequences followed by transrectal in-bore MRI-guided prostate biopsy. Maximum intensity projections (MIP) and DCE-CT perfusion parameters (CTP) were compared between healthy and malignant tissue. Two radiologists independently rated image quality and the tumor lesion delineation quality of PCa using a five-point ordinal scale. MIP and CTP were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. RESULTS: The PCa detection rate ranged between 57 to 79% for the two readers for DCE-CT and was 92% for DCE-MRI. DCE-CT perfusion parameters in PCa tissue in the PZ were significantly different compared to regular prostate tissue and benign lesions. Image quality and lesion visibility were comparable between DCE-CT and DCE-MRI (VGC: AUC 0.612 and 0.651, p>0.05). CONCLUSION: Our preliminary results suggest that it is feasible to use DCE-CT for identification and visualization, and subsequent segmentation for focal radiotherapy approaches to PCa

Simultaneous multiparametric functional positron emission tomography-magnetic resonance imaging of the prostate for improved diagnosis and advanced radiotherapy treatment planning

Für die Diagnose des Prostatakarzinoms (PCa) bei Patienten mit erhöhtem Serumspiegel an prostataspezifischem Antigen (PSA) und mit einer suspekten digitalen-rektalen Untersuchung war die transrectale, Ultraschall-gezielte Biopsie bisher die Methode der Wahl. Die Limitation dieser Biopsiemethode ist eine hohe Anzahl an falsch negativen Resultaten. Der erste Teil dieser Arbeit befasste sich mit einer alternativen Biopsiemethode, der Magnetresonanztomographie-(MRT)-gezielten Biopsie. Die Intention dieser Arbeit war es, die diagnostische Genauigkeit dieser Methode zu evaluieren und die Resultate mit der Literatur zu vergleichen. In unserem Patientenkollektiv wurde in 11/41 Patienten ein PCa diagnostiziert. Dieses Ergebnis war gering niedriger als in der Literatur, jedoch wurde während der Nachsorge bei Patienten mit einem negativen Biopsieergebnis kein neuerliches PCa entdeckt. Die MRT-gezielte Biopsie der Prostata ist somit eine verlässliche Methode mit hoher diagnostischer Genauigkeit. Mit der Etablierung der MRT der Prostata in der klinischen Routine kam die Frage auf, welche MRT-Parameter für ein adäquates lokales Staging des PCa notwendig sind. Die zweite Studie beschäftigte sich mit dem Mehrwert der Protonenspektroskopie (MRSI) zum Standard-MRT-Protokoll. In der Studie wurde die diagnostische Genauigkeit eines MRT-Protokolls mit drei Parametern (T2-w, diffusionsgewichtete (DWI) und Kontrastmittel-verstärkte Sequenzen) mit jener eines Protokolls mit vier Parametern (plus MRSI) verglichen. Darüberhinaus wurde der Vorhersagewert des Gleason Score bestimmt. Die Ergebnisse der Studie zeigten, dass ein Protokoll mit drei Parametern ohne MRSI die gleich hohe diagnostische Genauigkeit erreicht und auch der Gleason Score tendenziell vorhersehbar ist. Im Jahr 2012 wurde von der europäischen Gesellschaft für Uroradiologie die erste Version des Prostate Imaging Reporting and Data System (PI-RADS) publiziert, um eine standardisierte Befundung der Prostata zu ermöglichen. Um die Befundung weiter zu verbessern wurde 2015 eine neuere, verbesserte Version (PI-RADS v2) veröffentlicht. Die Studie in Kapitel vier behandelte einen Vergleich der Versionen v1 und v2 bezüglich ihrer diagnostischen Genauigkeit und Reproduzierbarkeit. Die Resultate zeigten, dass die neue Version besser für die Detektion von PCa in der Transitionszone geeignet ist, wohingegen die alte Version in der peripheren Zone besser abschneidet. Die Reproduzierbarkeit beider Versionen war nahezu perfekt. Um Informationen über die Tumorbiologie des PCa zu gewinnen ist die zusätzliche Rolle der Positronen-Emissionstomographie (PET) in Kombination mit der MRT noch nicht vollständig geklärt. Die nächste Studie befasste sich mit der Machbarkeit einer fusionierten multiparametrischen [11C]Acetat-PET/MRT für ein lokales und Ganzkörper-Staging. Die Resultate zeigten, dass diese Methode funktioniert und darüber hinaus zusätzliche Informationen über die Tumorbiologie basierend auf den „Hall marks of cancer“ liefert. Für das lokale Staging erreichte die Kombination von T2-w und DWI die höchste diagnostische Genauigkeit. Der Mehrwert der PET lag in der Detektion von Sekundaria, die nicht mit der MRT alleine entdeckt werden konnten. Das letzte Kapitel der Arbeit befasste sich mit Patienten mit einem biochemischen Rezidiv nach radikaler Prostatektomie und Verdacht auf Knochenmetastasen. Alle eingeschlossenen Patienten unterzogen sich einer [11C]Acetat-PET, sowie der bisherigen Standardmethode, der Knochenszintigraphie. Die Studie zeigte, dass die [11C]Acetat-PET eine verlässliche, mit der Szintigraphie vergleichbare Methode für die Detektion von Knochenmetastasen ist.For the detection of prostate cancer (PCa) in patients with elevated PSA levels, and who also have a suspicious digital rectal examination, the first-line biopsy method has been transrectal ultrasound biopsy. The limitation of this technique is that there are a higher number of false-negatives due to insufficient sampling of the prostate. Therefore, the first part of the thesis focuses on an alternative technique to overcome these limitations. In patients in whom PCa was suspected, an in-bore MR-guided prostate biopsy (MRGB) was performed. The purpose was to evaluate the diagnostic accuracy and to compare our results to those reported in the literature. In our patient cohort of 41 patients, 11 new PCa were found. These results were slightly lower compared to those in the literature, but, even more important in those patients with a negative MRGB, no new PCa was found during the follow-up period. This suggests that MRGB is a reliable diagnostic tool with a high diagnostic accuracy. With the establishment of prostate MRI in the clinical routine, the question was raised about which MRI parameters should be included for adequate local detection and staging of PCa. The second study included in this thesis deals with the additional value of magnetic resonance spectroscopy imaging (MRSI) in the examination protocol. MRSI is a time-consuming parameter in the MRI protocol. The additional benefit of MRSI has been controversially discussed. In our study, we compared the diagnostic accuracy of a sum score that included three MRI parameters (T2w, DCE, and DWI) versus a sum score with four parameters (additional MRSI). We also evaluated the performance of each score in predicting the Gleason grade. The results of the study showed that a shorter protocol without MRSI at 3Tesla(T) had the same diagnostic accuracy and had good potential for predicting the Gleason score. In 2012, the European Society for Urogenital Radiology published the first version of the prostate imaging reporting and data system (PI-RADS). The guidelines were designed to help standardize the reporting of prostate MRI. To further improve the reporting, a new version, the PIRADS v2, was published 2015. The next study included in Chapter 3 describes a head-to-head comparison of both versions, including inter-reader agreement for both versions to demonstrate the reproducibility. In that study, we evaluated the overall performance of both versions for the detection of PCa, and included a subtype analysis for the peripheral zone (PZ) and the transition zone (TZ) of the prostate. The results showed that the new version was more accurate for the detection of PCa in the TZ. In the PZ, v1 outperformed v2. The reproducibility was almost perfect for both versions. To provide insight into the tumor biology of PCa, the role of positron emission tomography (PET) in combination with MRI has not yet been fully exploited. The next study investigated the feasibility of fused multiparametric [11C]acetate PET-MRI (MP [11C]acetate PET-MRI) to investigate the value of MRI and PET parameters for primary PCa detection and local and distant staging. The results indicated that MP [11C]acetate PET-MRI was feasible and provided background information consistent with the hallmarks of cancer. For the local staging of PCa, the combination of the MRI-derived parameters, T2w and DWI, achieved the highest diagnostic accuracy. The additional benefit of PET was in the distant staging, and the identification of extra metastases not seen with MRI alone. The last chapter of my PhD thesis focuses on patients with biochemical recurrence after radical prostatectomy, due to PCa, in whom bone metastases are suspected. All included patients underwent [11C]acetate PET and bone scintigraphy. In our clinical study, [11C]acetate PET was a reliable tool for the detection of recurrence and especially for the detection of bone metastases. The performance of [11C]acetate PET was equivalent to that of bone scintigraphy.submitted by Stephan Helmuth Polanec MDZusammenfassung in deutscher SpracheAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Dissertation, 2016OeBB(VLID)171553

Breast lesions classified as probably benign (BI-RADS 3) on magnetic resonance imaging: a systematic review and meta-analysis

Purpose To investigate prevalence, malignancy rates, imaging features, and follow-up intervals for probably benign (BI-RADS 3) lesions on breast magnetic resonance imaging (MRI). Methods A systematic database-review of articles published through 22/06/2016 was performed. Eligible studies reported BI-RADS 3 lesions on breast MRI. Two independent reviewers performed a literature review and data extraction. Data collection included study characteristics, number/type of BI-RADS 3 lesions, final diagnosis (histopathology and/or follow-up). Sources of bias (QUADAS-2) were assessed. Meta-analysis included data-pooling, heterogeneity testing, and meta-regression. Results Fifteen studies were included. Prevalence was reported in 11 studies (range: 1.2-24.3%). Malignancy rates ranged between 0.5-10.1% (pooled 61/2814, 1.6%, 95%-CI:0.9-2.3% (random-effects-model), I2=53%, P=0.007). In a subgroup of 11 studies (2183 lesions), highest malignancy rates were observed in non-mass lesions (pooled 25/714, 2.3%, 95%-CI:0.8-3.9%, I2=52%, P=0.021) followed by mass lesions (pooled 15/771, 1.5%, 95%-CI:0.7-2.4%, I2=0%, P=0.929), and foci (pooled 10/698, 1%, 95%-CI:0.3-1.7%, I2=0%, P=0.800). There was non-significant negative association between prevalence and malignancy rates (P=0.077). Malignant lesions were diagnosed at all follow-up time points. Conclusion While prevalence of MRI BI-RADS 3 lesions was strongly heterogeneous, pooled malignancy rates met BI-RADS benchmarks (<2%). Malignancy rates varied, exceeding 2% in non-mass lesions. Twenty-four-month surveillance is required to detect all malignant lesions. Key points • Probably benign (BI-RADS 3) lesions showed a pooled malignancy-rate of 1.6% (95%-CI:0.9-2.3%). • Malignancy rates differ and are highest in non-mass lesions (2.3%, 95%-CI:0.8-3.9%). • The prevalence of BI-RADS 3 lesions on breast MRI ranged from 1.2-24.3%. • Malignant lesions were diagnosed at follow-up time points up to 24 months

Diffusion‐Weighted MRI of Breast Cancer: Improved Lesion Visibility and Image Quality Using Synthetic b‐Values

Background: Diffusion‐weighted imaging (DWI) is an MRI technique with the potential to serve as an unenhanced breast cancer detection tool. Synthetic b‐values produce images with high diffusion weighting to suppress residual background signal, while avoiding additional measurement times and reducing artifacts. Purpose: To compare acquired DWI images (at b = 850 s/mm2) and different synthetic b‐values (at b = 1000–2000 s/mm2) in terms of lesion visibility, image quality, and tumor‐to‐tissue contrast in patients with malignant breast tumors. Study Type: Retrospective. Population: Fifty‐three females with malignant breast lesions. Field Strength/Sequence: T2w, DWI EPI with STIR fat‐suppression, and dynamic contrast‐enhanced T1w at 3T. Assessment: From acquired images using b‐values of 50 and 850 s/mm2, synthetic images were calculated at b = 1000, 1200, 1400, 1600, 1800, and 2000 s/mm2. Four readers independently rated image quality, lesion visibility, preferred b‐value, as well as the lowest and highest b‐value, over the range of b‐values tested, to provide a diagnostic image. Statistical Tests: Medians and mean ranks were calculated and compared using the Friedman test and Wilcoxon signed‐rank test. Reproducibility was analyzed by intraclass correlation (ICC), Fleiss, and Cohen's κ. Results: Relative signal‐to‐noise and contrast‐to‐noise ratios decreased with increasing b‐values, while the signal‐intensity ratio between tumor and tissue increased significantly (P < 0.001). Intermediate b‐values (1200–1800 s/mm2) were rated best concerning image quality and lesion visibility; the preferred b‐value mostly lay at 1200–1600 s/mm2. Lowest and highest acceptable b‐values were 850 s/mm2 and 2000 s/mm2. Interreader agreement was moderate to high concerning image quality (ICC: 0.50–0.67) and lesion visibility (0.70–0.93), but poor concerning preferred and acceptable b‐values (κ = 0.032–0.446). Data Conclusion: Synthetically increased b‐values may be a way to improve tumor‐to‐tissue contrast, lesion visibility, and image quality of breast DWI, while avoiding the disadvantages of performing DWI at very high b‐values. Level of Evidence: 3 Technical Efficacy: Stage

Reliability of high-resolution ultrasound and magnetic resonance arthrography of the shoulder in patients with sports-related shoulder injuries.

INTRODUCTION:The shoulder, a very complex joint, offers a wide range of pathologies. Intraarticular abnormalities and rotator cuff injuries are mainly assessed and diagnosed by magnetic resonance arthrography (MRA). In contrast to this well-established gold standard, high-resolution ultrasound (US) offers an additional easy and excellent modality to assess the shoulder joint. Therefore, the purpose of this study was to evaluate in which anatomic structures and pathologies comparable results of US and MRA could be achieved. MATERIALS AND METHODS:In this IRB-approved prospective study 67 patients with clinically suspected labral lesions, rotator cuff rupture, or injury of the long head of the biceps (LHB) tendon were enrolled. Each participant was examined with high resolution US, and directly followed by MRA at 3 Tesla with a standard sequence protocol. To evaluate the agreement of the diagnostic performance between US and MRA a weighted kappa statistic was used. RESULTS:Both of the investigated modalities yielded a moderate to almost perfect agreement in assessing a wide range of shoulder joint pathologies. For the rotator cuff, consistency was found in 71.64% for the supraspinatus tendon, in 95.52% for the infraspinatus tendon, in 83.58% for the subscapularis tendon, and in 98.51% for the teres minor tendon. The diagnostic accuracy between both modalities was 80.60% for the LHB tendon, 77.61% for the posterior labroligamentous complex, 83.58% for the acromioclavicular joint, and 91.04% for the assessment of osseous irregularities and impaction fractures. CONCLUSIONS:High resolution US is a reliable imaging modality for the rotator cuff, the LHB tendon, and the acromioclavicular joint, so for these structures we recommend a preference for US over MRA based on its diagnostic accuracy, comfortability, cost effectiveness, and availability. If the diagnosis remains elusive, for all other intraarticular structures we recommend MRA for further diagnostic assessment

Objective measurement of breast density, a marker of breast cancer risk, using fully automated radiation- and compression-free MRI.

11088 Background: Women may have contraindications to mammography (MG) or simply refuse the test due to subjective reservations usually concerning compression and/or radiation. Other than the detection of suspicious findings these women do not have standardized information concerning their breast density (BD), one of the strongest independent predictors of breast cancer (BC) risk. We developed a fully-automated quantitative magnetic resonance imaging (MRI) based BD measurement system, provided correlation to MG BD estimation and compared BD in BC patients and age-matched healthy controls. Methods: In this IRB-approved prospective study 35 healthy women and 19 BC patients age-matched to one of the healthy controls were included. BD for healthy women and BC patients was assessed using a) subjective qualitative radiologist´s review allocating 1 of 4 ACR BIRADS BD categories, b) Cumulus, a MG based semi-automatic method and c) a radiation- and compression-free MRI measurements system, which automatically calculates volume of breast (cm3), % of fatty tissue and % of glandular tissue. Descriptive statistics were used to define the typical range of quantitative MRI BD readings corresponding to the qualitative four ACR BIRADS BD categories. Áppropriate statistical tests were used to compare mean values of method b) and c) and BD readings of cancers and controls. Results: % MRI BD correlated well with % MG BD (r = 0.83; P &lt; 0.0001). MRI BD measurements ranged from 1.7% to 61.9% (mean 29.05%). MG BD measurements ranged from 5.42% to 74.33% (mean 40.23%). Equivalent values were found with MRI BD readings of 0-7.2%, 7.3-26%, 26.1-39.6% and &gt;39.7% respectively for each of the four ACR BIRADS BD categories. Mean BD (%) was higher in BC patients than in healthy controls: 24% (SD 16.9%) vs. 18.4% (16.6). Conclusions: MRI BD measurement strongly correlates with MG based BD readings. The data suggest that objective, radiation- and compression-free MRI BD measurement is a convenient alternative to MG for assessment of BD. MRI BD measurement confirms higher breast density in BC patients compared to healthy women. The data is entirely consistent with the fact that BD is a strong independent risk factor for BC. </jats:p