Clinical utility of combined T2-weighted imaging and T2-mapping in the detection of prostate cancer: a multi-observer study

Background: To evaluate the clinical utility of combined T2-weighted imaging and T2-mapping for the detection of prostate cancer. Methods: Forty patients underwent multiparametric magnetic resonance imaging (mpMRI) and T2-mapping of the prostate. Three readers each reviewed two sets of images: T2-weighted fast spin-echo (FSE) sequence (standard T2), and standard T2 in combination with T2-mapping. Each reader assigned probability scores for malignancy to each zone [peripheral zone (PZ) or transition zone (TZ)]. Inter-observer variability for standard T2 and combined standard T2 with T2-mapping were assessed. Diagnostic accuracy was compared between standard T2 and combined standard T2 with T2-mapping. Results: There was fair agreement between all three readers for standard T2 [intraclass correlation coefficient (ICC) =0.56] and combined standard T2 with T2-mapping (ICC =0.58). There was no significant difference in the area under the receiver operator characteristics curve for standard T2 compared to combined standard T2 with T2-mapping (0.89 vs. 0.82, P=0.31). Sensitivity (Sn) for combined standard T2 with T2-mapping was significantly higher compared to standard T2 alone (73.0% vs. 49.2%, P=0.006). Specificity (Sp) for combined standard T2 with T2-mapping was borderline significantly lower compared to standard T2 alone (89.3% vs. 94.9%, P=0.05). There was no significant differences between the negative predictive values (NPVs) and positive predictive values (PPVs) (P=0.07, P=0.45). Conclusions: Combination of T2-weighted imaging and T2-mapping could potentially increase Sn for prostate malignancy compared to T2-weighted imaging alone

Beyond blood brain barrier breakdown – in vivo detection of occult neuroinflammatory foci by magnetic nanoparticles in high field MRI

BACKGROUND: Gadopentate dimeglumine (Gd-DTPA) enhanced magnetic resonance imaging (MRI) is widely applied for the visualization of blood brain barrier (BBB) breakdown in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the potential of magnetic nanoparticles to detect macrophage infiltration by MRI was demonstrated. We here investigated a new class of very small superparamagnetic iron oxide particles (VSOP) as novel contrast medium in murine adoptive-transfer EAE. METHODS: EAE was induced in 17 mice via transfer of proteolipid protein specific T cells. MR images were obtained before and after application of Gd-DTPA and VSOP on a 7 Tesla rodent MR scanner. The enhancement pattern of the two contrast agents was compared, and correlated to histology, including Prussian Blue staining for VSOP detection and immunofluorescent staining against IBA-1 to identify macrophages/microglia. RESULTS: Both contrast media depicted BBB breakdown in 42 lesions, although differing in plaques appearances and shapes. Furthermore, 13 lesions could be exclusively visualized by VSOP. In the subsequent histological analysis, VSOP was localized to microglia/macrophages, and also diffusely dispersed within the extracellular matrix. CONCLUSION: VSOP showed a higher sensitivity in detecting BBB alterations compared to Gd-DTPA enhanced MRI, providing complementary information of macrophage/microglia activity in inflammatory plaques that has not been visualized by conventional means

The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy

Background To explore the diagnostic benefit of an additional image fusion of the sagittal plane in addition to the standard axial image fusion, using a sensor-based MRI/US fusion platform. Methods During July 2013 and September 2015, 251 patients with at least one suspicious lesion on mpMRI (rated by PI- RADS) were included into the analysis. All patients underwent MRI/US targeted biopsy (TB) in combination with a 10 core systematic prostate biopsy (SB). All biopsies were performed on a sensor-based fusion system. Group A included 162 men who received TB by an axial MRI/US image fusion. Group B comprised 89 men in whom the TB was performed with an additional sagittal image fusion. Results The median age in group A was 67 years (IQR 61–72) and in group B 68 years (IQR 60–71). The median PSA level in group A was 8.10 ng/ml (IQR 6.05–14) and in group B 8.59 ng/ml (IQR 5.65–12.32). In group A the proportion of patients with a suspicious digital rectal examination (DRE) (14 vs. 29%, p = 0.007) and the proportion of primary biopsies (33 vs 46%, p = 0.046) were significantly lower. The rate of PI-RADS 3 lesions were overrepresented in group A compared to group B (19 vs. 9%; p = 0.044). Classified according to PI-RADS 3, 4 and 5, the detection rates of TB were 42, 48, 75% in group A and 25, 74, 90% in group B. The rate of PCa with a Gleason score ≥7 missed by TB was 33% (18 cases) in group A and 9% (5 cases) in group B; p-value 0.072. An explorative multivariate binary logistic regression analysis revealed that PI-RADS, a suspicious DRE and performing an additional sagittal image fusion were significant predictors for PCa detection in TB. 9 PCa were only detected by TB with sagittal fusion (sTB) and sTB identified 10 additional clinically significant PCa (Gleason ≥7). Conclusion Performing an additional sagittal image fusion besides the standard axial fusion appears to improve the accuracy of the sensor-based MRI/US fusion platform

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis vs. viral hepatitis assessed by MR elastography

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis (PSC) in comparison to viral hepatitis was assessed as a potential new biomarker using MR elastography (MRE). In this proof-of-concept study, we hypothesized a rather increased heterogeneity in PSC and a rather homogeneous distribution in viral hepatitis. Forty-six consecutive subjects (PSC: n=20, viral hepatitis: n=26) were prospectively enrolled between July 2014 and April 2017. Subjects underwent multifrequency MRE (1.5 T) using drive frequencies of 35-60 Hz and generating shear-wave speed (SWS in m/s) maps as a surrogate of stiffness. The coefficient of variation (CV in %) was determined to quantify fibrosis heterogeneity. Mean SWS and CV were 1.70 m/s and 21% for PSC, and 1.84 m/s and 18% for viral hepatitis. Fibrosis heterogeneity was significantly increased for PSC (P=0.04) while no difference was found for SWS of PSC and viral hepatitis (P=0.17). Global hepatic stiffness was similar in PSC and viral hepatitis groups, but spatial heterogeneity may reveal spatial patterns of stiffness changes towards enhanced biophysics-based diagnosis by MRI

A Randomized Controlled Comparison of Image Quality

Background The purpose of the present study was to compare the image quality of spinal magnetic resonance (MR) imaging performed on a high-field horizontal open versus a short-bore MR scanner in a randomized controlled study setup. Methods Altogether, 93 (80% women, mean age 53) consecutive patients underwent spine imaging after random assignement to a 1-T horizontal open MR scanner with a vertical magnetic field or a 1.5-T short-bore MR scanner. This patient subset was part of a larger cohort. Image quality was assessed by determining qualitative parameters, signal-to-noise (SNR) and contrast-to-noise ratios (CNR), and quantitative contour sharpness. Results The image quality parameters were higher for short-bore MR imaging. Regarding all sequences, the relative differences were 39% for the mean overall qualitative image quality, 53% for the mean SNR values, and 34–37% for the quantitative contour sharpness (P<0.0001). The CNR values were also higher for images obtained with the short-bore MR scanner. No sequence was of very poor (nondiagnostic) image quality. Scanning times were significantly longer for examinations performed on the open MR scanner (mean: 32±22 min versus 20±9 min; P<0.0001). Conclusions In this randomized controlled comparison of spinal MR imaging with an open versus a short-bore scanner, short-bore MR imaging revealed considerably higher image quality with shorter scanning times

Feasibility of Intestinal MR Elastography in Inflammatory Bowel Disease

Background: While MR enterography allows detection of inflammatory bowel disease (IBD), the findings continue to be of limited use in guiding treatment-medication vs. surgery. Purpose: To test the feasibility of MR elastography of the gut in healthy volunteers and IBD patients. Study type: Prospective pilot. Population: Forty subjects (healthy volunteers: n = 20, 37 ± 14 years, 10 women; IBD patients: n = 20 (ulcerative colitis n = 9, Crohn's disease n = 11), 41 ± 15 years, 11 women). Field strength/sequence: Multifrequency MR elastography using a single-shot spin-echo echo planar imaging sequence at 1.5 T with drive frequencies of 40, 50, 60, and 70 Hz. Assessment: Maps of shear-wave speed (SWS, in m/s) and loss angle (φ, in rad), representing stiffness and solid-fluid behavior, respectively, were generated using tomoelastography data processing. Histopathological analysis of surgical specimens was used as reference standard in patients. Statistical tests: Unpaired t-test, one-way analysis of variance followed by Tukey post hoc analysis, Pearson's correlation coefficient and area under the receiver operating characteristic curve (AUC) with 95%-confidence interval (CI). Significance level of 5%. Results: MR elastography was feasible in all 40 subjects (100% technical success rate). SWS and φ were significantly increased in IBD by 21% and 20% (IBD: 1.45 ± 0.14 m/s and 0.78 ± 0.12 rad; healthy volunteers: 1.20 ± 0.14 m/s and 0.65 ± 0.06 rad), whereas no significant differences were found between ulcerative colitis and Crohn's disease (P = 0.74 and 0.90, respectively). In a preliminary assessment, a high diagnostic accuracy in detecting IBD was suggested by an AUC of 0.90 (CI: 0.81-0.96) for SWS and 0.84 (CI: 0.71-0.95) for φ. Data conclusion: In this pilot study, our results demonstrated the feasibility of MR elastography of the gut and showed an excellent diagnostic performance in predicting IBD. Evidence level: 1 TECHNICAL EFFICACY: Stage 1

Comparison of non-invasive assessment of liver fibrosis in patients with alpha1-antitrypsin deficiency using magnetic resonance elastography (MRE), acoustic radiation force impulse (ARFI) Quantification, and 2D-shear wave elastography (2D-SWE)

Purpose: Although it has been known for decades that patients with alpha1-antitrypsin deficiency (AATD) have an increased risk of cirrhosis and hepatocellular carcinoma, limited data exist on non-invasive imaging-based methods for assessing liver fibrosis such as magnetic resonance elastography (MRE) and acoustic radiation force impulse (ARFI) quantification, and no data exist on 2D-shear wave elastography (2D-SWE). Therefore, the purpose of this study is to evaluate and compare the applicability of different elastography methods for the assessment of AATD-related liver fibrosis. Methods: Fifteen clinically asymptomatic AATD patients (11 homozygous PiZZ, 4 heterozygous PiMZ) and 16 matched healthy volunteers were examined using MRE and ARFI quantification. Additionally, patients were examined with 2D-SWE. Results: A high correlation is evident for the shear wave speed (SWS) determined with different elastography methods in AATD patients: 2D-SWE/MRE, ARFI quantification/2D-SWE, and ARFI quantification/MRE (R = 0.8587, 0.7425, and 0.6914, respectively; P <= 0.0089). Four AATD patients with pathologically increased SWS were consistently identified with all three methods-MRE, ARFI quantification, and 2D-SWE. Conclusion: The high correlation and consistent identification of patients with pathologically increased SWS using MRE, ARFI quantification, and 2D-SWE suggest that elastography has the potential to become a suitable imaging tool for the assessment of AATD-related liver fibrosis. These promising results provide motivation for further investigation of non-invasive assessment of AATD-related liver fibrosis using elastography

Dataset of prostate MRI annotated for anatomical zones and cancer

In the present work, we present a publicly available, expert-segmented representative dataset of 158 3.0 Tesla biparametric MRIs [1]. There is an increasing number of studies investigating prostate and prostate carcinoma segmentation using deep learning (DL) with 3D architectures [2], [3], [4], [5], [6], [7]. The development of robust and data-driven DL models for prostate segmentation and assessment is currently limited by the availability of openly available expert-annotated datasets [8], [9], [10]. The dataset contains 3.0 Tesla MRI images of the prostate of patients with suspected prostate cancer. Patients over 50 years of age who had a 3.0 Tesla MRI scan of the prostate that met PI-RADS version 2.1 technical standards were included. All patients received a subsequent biopsy or surgery so that the MRI diagnosis could be verified/matched with the histopathologic diagnosis. For patients who had undergone multiple MRIs, the last MRI, which was less than six months before biopsy/surgery, was included. All patients were examined at a German university hospital (Charité Universitätsmedizin Berlin) between 02/2016 and 01/2020. All MRI were acquired with two 3.0 Tesla MRI scanners (Siemens VIDA and Skyra, Siemens Healthineers, Erlangen, Germany). Axial T2W sequences and axial diffusion-weighted sequences (DWI) with apparent diffusion coefficient maps (ADC) were included in the data set. T2W sequences and ADC maps were annotated by two board-certified radiologists with 6 and 8 years of experience, respectively. For T2W sequences, the central gland (central zone and transitional zone) and peripheral zone were segmented. If areas of suspected prostate cancer (PIRADS score of ≥ 4) were identified on examination, they were segmented in both the T2W sequences and ADC maps. Because restricted diffusion is best seen in DWI images with high b-values, only these images were selected and all images with low b-values were discarded. Data were then anonymized and converted to NIfTI (Neuroimaging Informatics Technology Initiative) format

Design and Immunological Validation of Macaca fascicularis Papillomavirus Type 3 Based Vaccine Candidates in Outbred Mice: Basis for Future Testing of a Therapeutic Papillomavirus Vaccine in NHPs

Persistent human papillomavirus (HPV) infections are causative for cervical neoplasia and carcinomas. Despite the availability of prophylactic vaccines, morbidity and mortality induced by HPV are still too high. Thus, an efficient therapy, such as a therapeutic vaccine, is urgently required. Herein, we describe the development and validation of Macaca fascicularis papillomavirus type 3 (MfPV3) antigens delivered via nucleic-acid and adenoviral vectors in outbred mouse models. Ten artificially fused polypeptides comprising early viral regulatory proteins were designed and optionally linked to the T cell adjuvant MHC-II-associated invariant chain. Transfected HEK293 cells and A549 cells transduced with recombinant adenoviruses expressing the same panel of artificial antigens proved proper and comparable expression, respectively. Immunization of outbred CD1 and OF1 mice led to CD8+ and CD4+ T cell responses against MfPV3 antigens after DNA- and adenoviral vector delivery. Moreover, in vivo cytotoxicity of vaccine-induced CD8+ T cells was demonstrated in BALB/c mice by quantifying specific killing of transferred peptide-pulsed syngeneic target cells. The use of the invariant chain as T cell adjuvant enhanced the T cell responses regarding cytotoxicity and in vitro analysis suggested an accelerated turnover of the antigens as causative. Notably, the fusion-polypeptide elicited the same level of T-cell responses as administration of the antigens individually, suggesting no loss of immunogenicity by fusing multiple proteins in one vaccine construct. These data support further development of the vaccine candidates in a follow up efficacy study in persistently infected Macaca fascicularis monkeys to assess their potential to eliminate pre-malignant papillomavirus infections, eventually instructing the design of an analogous therapeutic HPV vaccine