Synthetic magnetic resonance imaging for primary prostate cancer evaluation:Diagnostic potential of a non-contrast-enhanced bi-parametric approach enhanced with relaxometry measurements

PURPOSE: Bi-parametric magnetic resonance imaging (bpMRI) with diffusion-weighted images has wide utility in diagnosing clinically significant prostate cancer (csPCa). However, bpMRI yields more false-negatives for PI-RADS category 3 lesions than multiparametric (mp)MRI with dynamic-contrast-enhanced (DCE)-MRI. We investigated the utility of synthetic MRI with relaxometry maps for bpMRI-based diagnosis of csPCa. METHODS: One hundred and five treatment-naïve patients who underwent mpMRI and synthetic MRI before prostate biopsy for suspected PCa between August 2019 and December 2020 were prospectively included. Three experts and three basic prostate radiologists evaluated the diagnostic performance of conventional bpMRI and synthetic bpMRI for csPCa. PI-RADS version 2.1 category 3 lesions were identified by consensus, and relaxometry measurements (T1-value, T2-value, and proton density [PD]) were performed. The diagnostic performance of relaxometry measurements for PI-RADS category 3 lesions in peripheral zone was compared with that of DCE-MRI. Histopathological evaluation results were used as the reference standard. Statistical analysis was performed using the areas under the receiver operating characteristic curve (AUC) and McNemar test. RESULTS: In 102 patients without significant MRI artefacts, the diagnostic performance of conventional bpMRI was not significantly different from that of synthetic bpMRI for all readers (p = 0.11–0.79). The AUCs of the combination of T1-value, T2-value, and PD (T1 + T2 + PD) for csPCa in peripheral zone for PI-RADS category 3 lesions were 0.85 for expert and 0.86 for basic radiologists, with no significant difference between T1 + T2 + PD and DCE-MRI for both expert and basic radiologists (p = 0.29–0.45). CONCLUSION: Synthetic MRI with relaxometry maps shows promise for contrast media-free evaluation of csPCa

Clinical utility of the Vesical Imaging-Reporting and Data System for muscle-invasive bladder cancer between radiologists and urologists based on multiparametric MRI including 3D FSE T2-weighted acquisitions

Objectives: To investigate the clinical utility of the Vesical Imaging-Reporting and Data System (VI-RADS) by comparing its diagnostic performance for muscle-invasive bladder cancer (MIBC) between radiologists and urologists based on multiparametric MRI, including three-dimensional (3D) fast spin-echo (FSE) T2-weighted acquisitions. Methods: This study included 66 treatment-naïve patients (60 men, 6 women; mean age 74.0 years) with pathologically proven bladder cancer who underwent multiparametric MRI, including 3D FSE T2-weighted imaging, before transurethral bladder tumour resection between January 2010 and November 2018. The MRI scans were categorised according to the five-point VI-RADS score by four independent readers (two board-certified radiologists and board-certified urologists each), blinded to the histopathological findings. The VI-RADS scores were compared with the postoperative histopathological diagnosis. Interobserver agreement was assessed using weighted kappa coefficients. ROC analysis and generalised estimating equations were used to evaluate the diagnostic performance. Results: Forty-nine (74.2%) and 17 (25.8%) tumours were confirmed to be non-MIBC and MIBC, respectively, based on pathological examination. The interobserver agreement was good-to-excellent between all pairs of readers (range, 0.73–0.91). The urologists’ sensitivity/specificity values for DCE-MRI VI-RADS scores were significantly lower than those of radiologists. No significant differences were observed for the overall VI-RADS score. The AUC for the overall VI-RADS score was 0.94, 0.92, 0.89, and 0.87 for radiologists 1 and 2 and urologists 1 and 2, respectively. Conclusions: The VI-RADS score, based on multiparametric MRI including 3D FSE T2-weighted acquisitions, can be useful for radiologists and urologists to determine the bladder cancer muscle invasion status preoperatively. Key Points: • VI-RADS (using multiparametric MRI including 3D FSE T2-weighted acquisitions) achieves good to excellent interobserver agreement and has similar diagnostic performance for detecting muscle invasion by both radiologists and urologists. • The diagnostic performance of the overall VI-RADS score is high for both radiologists and urologists, particularly due to the dominant effect of diffusion-weighted imaging on the overall VI-RADS score. • The sensitivity and specificity values of the T2WI VI-RADS scores for four readers in our study (using 3D FSE T2-weighted acquisitions) were similar (with slightly higher specificity values) to previously published results (using 2D FSE T2-weighted acquisitions)

Tubular cell loss in early <i>inv/nphp2</i> mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation

<div><p>Inversion of embryonic turning (<i>inv</i>) cystic mice develop multiple renal cysts and are a model for type II nephronophthisis (NPHP2). The defect of planar cell polarity (PCP) by oriented cell division was proposed as the underlying cellular phenotype, while abnormal cell proliferation and apoptosis occur in some polycystic kidney disease models. However, how these cystogenic phenotypes are linked and what is most critical for cystogenesis remain largely unknown. In particular, in early cortical cytogenesis in the <i>inv</i> mutant cystic model, it remains uncertain whether the increased proliferation index results from changes in cell cycle length or cell fate determination. To address tubular cell kinetics, doubling time and total number of tubular cells, as well as amount of genomic DNA (gDNA), were measured in mutant and normal control kidneys. Despite a significantly higher bromodeoxyuridine (BrdU)-proliferation index in the mutant, total tubular cell number and doubling time were unaffected. Unexpectedly, the mutant had tubular cell loss, characterized by a temporal decrease in tubular cells incorporating 5-ethynyl-2´-deoxyuridine (EdU) and significantly increased nuclear debris. Based on current data we established a new multi-population shift model in postnatal renal development, indicating that a few restricted tubular cell populations contribute to cortical tubular formation. As in the <i>inv</i> mutant phenotype, the model simulation revealed a large population of tubular cells with rapid cell cycling and tubular cell loss. The proposed cellular kinetics suggest not only the underlying mechanism of the <i>inv</i> mutant phenotype but also a possible renal homeostatic mechanism for tubule formation.</p></div

Definition of mathematical parameters for the multiple proliferation model.

<p>Definition of mathematical parameters for the multiple proliferation model.</p

Double proliferation indexes in tubular cells from control and <i>inv</i>DC renal cortices.

<p>Double proliferation indexes in tubular cells from control and <i>inv</i>DC renal cortices.</p

Luminal nuclear protrusion and debris were linked to early cortical cystogenesis in <i>inv</i>DC kidneys.

<p><b>(a)</b> There were no TUNEL-positive (FITC green) tubular cells in the cortex at P15. Nuclei with incorporated EdU (cyan) (yellow arrows) and DAPI staining (blue) were visualized. <b>(b)</b> Luminal nuclear debris (yellow arrows) and protruding cells (white arrows) in tubules during early cystogenesis at P10. Incorporated EdU (cyan) or BrdU (magenta) was visualized with nuclear staining with DAPI (blue) and LTL (green). The EdU/BrdU double-labeled cells (white arrows) were often observed with apical nuclear protrusions. <b>(c)</b> The percentages of luminal debris or (<b>d</b>) the percentages of cells with apical nuclear protrusions per total tubular cells at the indicated postnatal mice age (control: n = 1721 at P11, n = 1795 at P14, n = 2200 at P17; <i>inv</i>DC mutant: n = 1886 at P11, n = 1866 at P14, n = 2155 at P17). <i>p <</i> 0.01 in comparison to the all control group are considered significant using a Fisher’s Chi-square test.</p

Decreased number of EdU-labeled tubular cells indicated possible tubular loss during early cystogenesis in <i>inv</i>DC kidneys.

<p><b>(a)</b> Scheme of the EdU/BrdU double-labeling experiment. EdU was injected intraperitoneally into the mice at P8, followed by multiple BrdU injections at 6 h and 12 h before the indicated harvesting days to increase the detectability of double-labeled cells. After isolation of kidneys, EdU and BrdU staining were performed sequentially as described in Materials and Methods. Tubular cells in the renal cortex of mice with each age (n = 3) were evaluated for double labeling experiments. <b>(b)</b> Quantitative data showing that there was no overall shift in cell cycle pattern during postnatal renal development between control and mutant mice at P11 and P14. It is noticed that the percentage of EdU/BrdU double positive cells was significantly elevated in mutant at P17. <b>(c)</b> Time-dependent decline of the percentages of EdU-positive tubular cells per total tubular cells in the early cystic kidneys. (*<i>P</i> < 0.05, Fisher’s Chi-squared test).</p

Expression of pH3 and γH2AX in nuclear protrusions.

<p><b>(a)</b> Luminal nuclear debris bound to precystic tubules in <i>inv</i>DC mutant at P15 (light inset). The nuclear protrusions were predominantly pH3-positive (magenta). (<b>b</b>) γH2AX expression in nuclear protrusions or sloughing cells with a dotted staining pattern in mutant tubular cells. Right column images were merged with F-actin (white) and DAPI (blue) staining. Scale bar, 20 μm (white). <b>(c)</b> γH2AX is a marker of S/G2 phase cell cycle in both controls and mutant renal tubules (left graph). Significant difference of total or single γH2AX expression ratio between controls and mutants (middle and right graph). *<i>P</i> < 0.05, Fisher’s Chi-squared test.</p