E Johnston

Textural analysis of multiparametric MRI detects transition zone prostate cancer

AbstractObjectivesTo evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour.MethodsSixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had ‘significant’ TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis.ResultsADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83).ConclusionTextural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion.Key Points• MR textural features of prostate transition zone may discriminate significant prostatic cancer. • Transition zone (TZ) containing significant tumour demonstrates a less peaked ADC histogram. • TZ containing significant tumour reveals higher post-contrast T1-weighted homogeneity. • The utility of MR texture analysis in prostate cancer merits further investigation.

The role of multi-parametric Mri in loco-regional staging of men diagnosed with early prostate cancer

Purpose of review To review the use of multi-parametric MRI (mpMRI) in loco-regional assessment of men with early prostate cancer. Recent findings mpMRI comprises anatomic T2 and T1 sequences supplemented by functional imaging techniques such as diffusion-weighted and dynamic contrast enhanced (DCE) imaging. mpMRI is gaining increasing acceptance for prostate cancer detection and staging of early disease. It can facilitate targeted therapies, guide surgical options and enable active surveillance within suitable patients. The technique can be performed at 1.5 or 3 Tesla, but sequence optimization is critical to successful implementation of mpMRI. T2 and diffusion-weighted sequences are minimal requirements and are often complemented by DCE images. When performed at high spatial resolution, DCE facilitates detection of disease, as well as assessment of extra-capsular extension, distal urethral sphincter and seminal vesicles involvement. Pre-biopsy mpMRI is recommended for both detection and staging as it avoids biopsy artefact, and when normal, has a negative predictive value of 95% for significant cancer. Summary mpMRI reliably detects clinically significant prostate tumour and ideally should be performed prior to biopsy. It provides an accurate method for local disease staging and facilitates a growing range of treatment options for patients with early disease.

Intratumoural evolutionary landscape of high-risk prostate cancer: The PROGENY study of genomic and immune parameters

Abstract Background Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. Patients and methods Forty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy. Seventy-nine tumour regions from 25 patients with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. Results We demonstrated extensive somatic nucleotide variation and somatic copy number alteration heterogeneity in high-risk PC. Overall, the mutational burden was low (0.93/Megabase), but two patients had hypermutation, with loss of mismatch repair (MMR) proteins, MSH2 and MSH6. Somatic copy number alteration burden was higher in patients with metastatic hormone-naive PC (mHNPC) than in those with high-risk localised PC (hrlPC), independent of Gleason grade. Mutations were rarely ubiquitous and mutational frequencies were similar for mHNPC and hrlPC patients. Enrichment of focal 3q26.2 and 3q21.3, regions containing putative metastasis drivers, was seen in mHNPC patients. We found evidence of parallel evolution with three separate clones containing activating mutations of β-catenin in a single patient. We demonstrated extensive intratumoural and intertumoural T-cell heterogeneity and high inflammatory infiltrate in the MMR-deficient (MMRD) patients and the patient with parallel evolution of β-catenin. Analysis of all patients with activating Wnt/β-catenin mutations demonstrated a low CD8+/FOXP3+ ratio, a potential surrogate marker of immune evasion. Conclusions The PROGENY (PROstate cancer GENomic heterogeneitY) study provides a diagnostic platform suitable for studying tumour ITH. Genetic aberrations in clinically high-risk PC are associated with altered patterns of immune infiltrate in tumours. Activating mutations of Wnt/β-catenin signalling pathway or MMRD could be considered as potential biomarkers for immunomodulation therapies. Clinical Trials.gov Identifier NCT02022371

Apparatus for Histological Validation of In Vivo and Ex Vivo Magnetic Resonance Imaging of the Human Prostate

This article describes apparatus to aid histological validation of magnetic resonance imaging studies of the human prostate. The apparatus includes a 3D-printed patient-specific mold that facilitates aligned in vivo and ex vivo imaging, in situ tissue fixation, and tissue sectioning with minimal organ deformation. The mold and a dedicated container include MRI-visible landmarks to enable consistent tissue positioning and minimize image registration complexity. The inclusion of high spatial resolution ex vivo imaging aids in registration of in vivo MRI and histopathology data.

Characterizing indeterminate (Likert-score 3/5) peripheral zone prostate lesions with PSA density, PI-RADS scoring and qualitative descriptors on multiparametric MRI

OBJECTIVE To determine whether indeterminate (Likert-score 3/5) peripheral zone (PZ) multiparametric MRI (mpMRI) studies are classifiable by prostate-specific antigen (PSA), PSA density (PSAD), Prostate Imaging Reporting And Data System version 2 (PI-RADS_v2) rescoring and morphological MRI features. METHODS Men with maximum Likert-score 3/5 within their PZ were retrospectively selected from 330 patients who prospectively underwent prostate mpMRI (3 T) without an endorectal coil, followed by 20-zone transperineal template prostate mapping biopsies ＋/- focal lesion-targeted biopsy. PSAD was calculated using pre-biopsy PSA and MRI-derived volume. Two readers A and B independently assessed included men with both Likert-assessment and PI-RADS_v2. Both readers then classified mpMRI morphological features in consensus. Men were divided into two groups: significant cancer (≥ Gleason 3 ＋ 4) or insignificant cancer (≤ Gleason 3 ＋ 3)/no cancer. Comparisons between groups were made separately for PSA & PSAD using Mann-Whitney test and morphological descriptors with Fishers exact test. PI-RADS_v2 and Likert-assessment were descriptively compared and percentage inter-reader agreement calculated. RESULTS 76 males were eligible for PSA & PSAD analyses, 71 for PI-RADS scoring, and 67 for morphological assessment (excluding significant image artefacts). Unlike PSA (p = 0.915), PSAD was statistically different (p = 0.004) between the significant [median: 0.19 ng ml-2 (interquartile range: 0.13-0.29)] and non-significant/no cancer [median: 0.13 ng ml-2 (interquartile range: 0.10-0.17)] groups. Presence of mpMRI morphological features was not significantly different between groups. Subjective Likert-assessment discriminated patients with significant cancer better than PI-RADS_v2. Inter-reader percentage agreement was 83% for subjective Likert-assessment and 56% for PI-RADS_v2. CONCLUSION PSAD may categorize presence of significant cancer in patients with Likert-scored 3/5 PZ mpMRI findings. Advances in knowledge: PSAD may be used in indeterminate PZ mpMRI to guide decisions between biopsy vs monitoring.

VERDICT Prostate Parameter Estimation with AMICO

The VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumours) technique estimates non-invasively cancer microstructure features. The clinical application of VERDICT for prostate cancer requires constraining some of the model’s parameter. This work uses the Accelerated Microstructure Imaging via Convex Optimization (AMICO) formulation for VERDICT (VERDICT-AMICO), to investigate parameter estimation for prostate tissue in an attempt to minimize the parameter constraints. We examine various dictionaries for VERDICT-AMICO enabling different levels of flexibility on the choice of parameter values. Depending on the stability of the fitting this procedure leads to the selection of a dictionary (or dictionaries) with the fewest number of model parameter constraints. Results show that with the current VERDICT imaging acquisition, the model can have an extra free parameter to fit, the extracellular diffusivity. In conclusion, the AMICO adaptation for VERDICT allowed testing of different values for the previously fixed model parameters, and helped relax assumptions of fixed extracellular diffusivity that the model currently uses for prostate cancer characterisation.