Normal Transition Zone Research Articles

The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture.

Cilia are essential organelles and variants in genes governing ciliary function result in ciliopathic diseases. The Ciliogenesis and PLANar polarity Effectors (CPLANE) protein complex is essential for ciliogenesis in animals models but remains poorly defined. Notably, all but one subunit of the CPLANE complex have been implicated in human ciliopathy. Here, we identify three families in which variants in the remaining CPLANE subunit CPLANE2/RSG1 also cause ciliopathy. These patients display cleft palate, tongue lobulations and polydactyly, phenotypes characteristic of Oral-Facial-Digital Syndrome. We further show that these alleles disrupt two vital steps of ciliogenesis, basal body docking and recruitment of intraflagellar transport proteins. Moreover, APMS reveals that Rsg1 binds the CPLANE and also the transition zone protein Fam92 in a GTP-dependent manner. Finally, we show that CPLANE is generally required for normal transition zone architecture. Our work demonstrates that CPLANE2/RSG1 is a causative gene for human ciliopathy and also sheds new light on the mechanisms of ciliary transition zone assembly.

Chemical Structure Evolution of Thermally Altered Coal during the Preparation of Coal-Based Graphene and Division of Thermally Altered Zone: Based on FTIR and Raman.

A suite of coal samples near a diabase dike was collected to investigate the structural and functional group evolution of a series of carbon materials prepared from thermally altered coals, explore the influence of thermal metamorphism distance on the structure of coal and its carbon material products, and divide the thermally altered zones. Using Fourier transform infrared and Raman studies, it was found that after demineralization, the aromatic parameters f ar H and I of the coal structure slightly increase, while the aliphatic parameters CH2/CH3 and oxidation parameter 'C' slightly decrease, and the degree of order of the coal structure increases. Graphitization can greatly improve aromatic parameters, eliminate aliphatic structures, and enhance orderliness. However, after oxidation and reduction, the aromatic parameters and ordering degree of graphene decrease. Except for the sample closely attached to the dike, the coal-based graphene yield of the other samples first decreases and then stabilizes with the increase of distance from the dike, which is consistent with the trend of changes in the reflectance of raw coal. The thermally altered distance affects the structural changes of coal and carbon material products. The coal attached to the dike has been damaged and polluted, and the aromaticity and orderliness of the prepared carbon material products are relatively poor. The aromaticity and orderliness of coal-based products prepared from other thermally altered coals are relatively high and increase with the closer the thermally altered distance. Based on the characterized parameters of coal samples and products with distance from the dike, the sampling area is divided into four zones, including abnormally altered zone, normal altered zone, transition zone, and original coal zone. Among them, the yield and quality of coal-based graphene prepared from coal in the normal altered zone are the highest, an ideal raw material collection area for making coal-based graphene.

Velocity structure (1D) and earthquakes relocation in the flat-slab to normal plate transition zone in the Argentinean transarc

The Argentinean Andean foreland region between latitudes 31°S to 33.5°S presents an intense crustal and upper mantle seismic activity that was recorded by a local seismological network called CHARSME (Chile Argentina SeisMic Experiment), and was used to obtain new velocity determinations. In a first moment, from 4 P-wave velocity (VP) models proposed by other authors, the detail in the layers was increased, resulting in better models used as initial model in the investment. Finally, by carefully selecting a set of earthquakes, a simultaneous velocity inversion, hypocentre determination and station correction were performed using the VELEST code. In order to obtain better velocity models (VP and VS) and VP/VS ratio, different tests were carried out in all processes.The final VP model presented in this paper incorporates considerations made in other seismological studies. This model accurately determined velocities between 10 and 65 km depth. The upper mantle velocity (VP) was defined in 8.05 km/s. From the Wadatti diagram, which represents a line whose slope is related to the wave velocities and the Poisson's coefficient, a VP/VS value of 1.732 was obtained. Alternative VP/VS values were also considered to invert VP, VS and VP/VS simultaneously. The minimum detailed model of VP, VS and VP/VS decreased the RMS by 25% relative to the initial models, implying an improvement in the uncertainty of locations. The new and precise locations of crustal earthquakes allowed defining clusters within Cuyania, a tectonic terrain that collided to Gondwana in the Early Paleozoic. Although it is known that foreland seismicity is mainly concentrated in this terrain, this work shows that there are well-defined zones within Cuyania that are more seismically active. Earthquakes of intermediate depth (upper mantle) are strongly agglomerated in the flat-slab zone of the subducting Nazca Plate.The discontinuities present in our model suggest upper, middle and lower crustal structuring, as well as a marked contrast between the sediments and the underlying basement. It was possible to interpret an upper crust consisting of sediments and basement to a depth of 25 km, a middle crust between 25 and 45 km and a lower crust between 45 and 55 km. We also defined the Mohorovičić (Moho) discontinuity at 55 km depth. The crustal velocities are in agreement with previous seismological studies.

Characterization of endoscopic features and histology of a distinct mucosal transition zone on the ileocecal valve (withvideo).

We have endoscopically encountered a zone of transitional mucosa between the colonic and ileal mucosa located in a 3- to 10-mm-wide ring around the ileocecal valve (ICV) orifice. We aimed to describe the features of the ICV transitional zone mucosa. We used videos and photographs from normal ICVs and biopsy samples from normal colonic mucosa, transitional zone mucosa, and normal ileal mucosa to characterize the endoscopic and histologic features of the ICV transitional zone mucosa. The ICV transitional zone is identifiable on every ICV without a circumferential adenoma or inflammation that obliterates the zone. The zone is characterized endoscopically by an absence of villi, which distinguishes it from the ileal mucosa, but the pits are more tubular and with more prominent blood vessels compared with normal colonic mucosa. Histologically, the villi of the transitional zone are blunted, and the amount of lymphoid tissue is intermediate between the colonic mucosa and ileal mucosa. This is the first description of the normal transitional zone of mucosa on the ICV. This zone has unique endoscopic features that should be recognized by colonoscopists and that can potentially create difficulty in identifying the margins of adenomas located on the ICV.

Test-retest repeatability of ADC in prostate using the multi b-Value VERDICT acquisition

PurposeVERDICT (Vascular, Extracellular, Restricted Diffusion for Cytometry in Tumours) MRI is a multi b-value, variable diffusion time DWI sequence that allows generation of ADC maps from different b-value and diffusion time combinations. The aim was to assess precision of prostate ADC measurements from varying b-value combinations using VERDICT and determine which protocol provides the most repeatable ADC. Materials and MethodsForty-one men (median age: 67.7 years) from a prior prospective VERDICT study (April 2016–October 2017) were analysed retrospectively. Men who were suspected of prostate cancer and scanned twice using VERDICT were included. ADC maps were formed using 5b-value combinations and the within-subject standard deviations (wSD) were calculated per ADC map. Three anatomical locations were analysed per subject: normal TZ (transition zone), normal PZ (peripheral zone), and index lesions. Repeated measures ANOVAs showed which b-value range had the lowest wSD, Spearman correlation and generalized linear model regression analysis determined whether wSD was related to ADC magnitude and ROI size. ResultsThe mean lesion ADC for b0b1500 had the lowest wSD in most zones (0.18–0.58x10-4 mm2/s). The wSD was unaffected by ADC magnitude (Lesion: p = 0.064, TZ: p = 0.368, PZ: p = 0.072) and lesion Likert score (p = 0.95). wSD showed a decrease with ROI size pooled over zones (p = 0.019, adjusted regression coefficient = -1.6x10-3, larger ROIs for TZ versus PZ versus lesions). ADC maps formed with a maximum b-value of 500 s/mm2 had the largest wSDs (1.90–10.24x10-4 mm2/s). ConclusionADC maps generated from b0b1500 have better repeatability in normal TZ, normal PZ, and index lesions.

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

Mechanical behaviour of glass-mortar under uniaxial compression loading based on a meso-scale modelling approach

Waste glass has become one of the most attractive candidates for replacing natural aggregate in mortar/concrete. Although researchers have conducted extensive experiments to investigate the macroscopic behaviour of mortar/concrete containing glass aggregate, certain mechanical behaviours are difficult to capture. These include damage initiation and propagation, and the effects of the intrinsic characteristics of glass aggregate, which are important in building applications. In this study, a two-dimensional meso-scale model was developed to numerically investigate the macroscopic and mesoscopic behaviour of glass mortar under uniaxial compression loading. Glass mortar was modelled as a three-phase composite including the surrounding normal mortar, glass aggregate and interfacial transition zone. The developed model was validated using experimental observations of the behaviour of glass mortar under uniaxial compression loading. Two prominent physical characteristics of glass aggregate were reflected in the developed meso-scale model, namely the angular aggregate shape and weaker interfacial transition zone. Based on the simulation results, it was found that both characteristics affected the mechanical response, while the aggregate shape was observed to be less significant. A comprehensive sensitivity analysis was performed to investigate the effects of various aggregate's properties, including random distribution, volume fraction, particle size, and elongation ratio, on the mechanical response of mortar. Overall, the developed meso-scale model for glass mortar is expected to provide a better understanding of the failure mechanisms of glass mortar/concrete under uniaxial compression loading.

Magnetic resonance fingerprinting in prostate cancer before and after contrast enhancement.

To assess the apparent diffusion coefficient (ADC) values and the T1 and T2 values derived from nonenhanced (NE) and contrast-enhanced (CE) magnetic resonance fingerprinting (MRF) in the prostate gland and to evaluate differences in values among prostate cancer, the normal peripheral zone (PZ) and the normal transition zone (TZ). Fifty-seven patients (median age, 73 years; range, 48-86) with prostate cancer who underwent multiparametric MRI including NE and CE MRF were included in this study. T1 and T2 values were extracted from NE and CE MRF, respectively. Five quantitative values (the ADC, NE T1, NE T2, CE T1 and CE T2 values) were measured in three areas: prostate cancer, PZ and TZ. We compared the values among the three areas and evaluated the differences between NE MRF and CE MRF values. ADC values and MRF-derived values were significantly higher in PZ than prostate cancer or TZ (p < 0.001). TZ had a significantly lower CE T1 but significantly higher values of the other variables than prostate cancer (p < 0.001). The T1 values in all three areas and the T2 values in prostate cancer and TZ were significantly lower on CE MRF than on NE MRF (p < 0.001). Quantitative analysis of NE and CE MRI can be conducted by using the MRF technique. The ADC value and the T1 and T2 values from CE MRF and NE MRF were found to be significantly different between prostate cancer and normal prostate tissue. The T1 and T2 values from contrast-enhanced MR fingerprinting are significantly different between prostate cancer and normal prostate tissue.

SUN-747 Steroid Hormone Metabolism Mediated Racial Disparity in Men with Benign Prostatic Hyperplasia

Introduction and Objective: Racial disparity in prostate cancer has been well established, with African American (AA) men having higher rates of diagnoses and death from the disease compared to Caucasian American (CA) men. AA men also have a high incidence of benign prostatic hyperplasia (BPH), a disease associated with lower urinary tract symptoms (LUTS) that affect >210 million men worldwide. Furthermore, AA men with BPH have an increased incidence of non-surgical treatment failure, larger prostates at time of surgery, and surgery occurring at a younger age. The use of selective estrogen receptor modulators (SERMs) in the treatment of BPH has been proposed, as an increase in ERα has been associated with disease progression. AA men have higher levels of circulating estrogens as compared to CA leading to an increased prenatal exposure to estrogens. Estrogen exposure has been shown to alter the epigenetic landscape of genes, and this prenatal exposure to estrogens could sensitize the AA men to altered steroid homeostasis leading to an increase susceptibility to BPH and an altered response to treatment. In this study, we examine the prostate expression and localization changes in estrogen receptors (ERα, ERβ) as well as steroid metabolism genes in AA and CA with or without BPH. Methods: To examine the impact of race on BPH, we examined prostate tissue from 66 men. We utilized 21 normal transition zone controls from radical prostatectomies, 8 normal transition zone controls from organ donors, and 37 BPH samples divided between CA and AA men. Using multispectral quantitative multiplex IHC, we examined the steroid hormone related protein expression of ERα, ERβ, CYP7B1, and AKR1C1 on each FFPE tissue section. We quantified the optical density of each protein of interest as well as examined colocalization and coexpression through cell and tissue segmentation. Results: In CA men, there is a dysregulation of ERα:ERβ homeostasis with BPH relative to normal as an increase in ERα and a decrease in ERβ expression was observed. Furthermore, an increase in CYP7B1, an enzyme that degrades ERβ ligands, was also observed. In AA men, we observed no difference between normal and BPH states, however in both normal and BPH prostate tissues, ERα and ERβ were increased relative to CA men. In addition, there is a decrease in AKR1C1, the enzyme that metabolizes DHT to an ERβ ligand. Conclusions: Our study supports the concept that differences in hormone pathways exist between AA and CA men. Understanding how these racial difference in steroid metabolism enzymes as well as ERs between CA and AA men with BPH could enhance treatment strategies for men with BPH.

Removing rician bias in diffusional kurtosis of the prostate using real‐data reconstruction

PurposeTo compare prostate diffusional kurtosis imaging (DKI) metrics generated using phase‐corrected real data with those generated using magnitude data with and without noise compensation (NC).MethodsDiffusion‐weighted images were acquired at 3T in 16 prostate cancer patients, measuring 6 b‐values (0‐1500 s/mm2), each acquired with 6 signal averages along 3 diffusion directions, with noise‐only images acquired to allow NC. In addition to conventional magnitude averaging, phase‐corrected real data were averaged in an attempt to reduce rician noise‐bias, with a range of phase‐correction low‐pass filter (LPF) sizes (8‐128 pixels) tested. Each method was also tested using simulations. Pixelwise maps of apparent diffusion (D) and apparent kurtosis (K) were calculated for magnitude data with and without NC and phase‐corrected real data. Average values were compared in tumor, normal transition zone (NTZ), and normal peripheral zone (NPZ).ResultsSimulations indicated LPF size can strongly affect K metrics, where 64‐pixel LPFs produced accurate metrics. Relative to metrics estimated from magnitude data without NC, median NC K were lower (P < 0.0001) by 6/11/8% in tumor/NPZ/NTZ, 64‐LPF real‐data K were lower (P < 0.0001) by 4/10/7%, respectively.ConclusionCompared with magnitude data with NC, phase‐corrected real data can produce similar K, although the choice of phase‐correction LPF should be chosen carefully.

MR Fingerprinting and ADC Mapping for Characterization of Lesions in the Transition Zone of the Prostate Gland.

BackgroundPreliminary studies have shown that MR fingerprinting-based relaxometry combined with apparent diffusion coefficient (ADC) mapping can be used to differentiate normal peripheral zone from prostate cancer and prostatitis. The utility of relaxometry and ADC mapping for the transition zone (TZ) is unknown.PurposeTo evaluate the utility of MR fingerprinting combined with ADC mapping for characterizing TZ lesions.Materials and MethodsTZ lesions that were suspicious for cancer in men who underwent MRI with T2-weighted imaging and ADC mapping (b values, 50-1400 sec/mm2), MR fingerprinting with steady-state free precession, and targeted biopsy (60 in-gantry and 15 cognitive targeting) between September 2014 and August 2018 in a single university hospital were retrospectively analyzed. Two radiologists blinded to Prostate Imaging Reporting and Data System (PI-RADS) scores and pathologic diagnosis drew regions of interest on cancer-suspicious lesions and contralateral visually normal TZs (NTZs) on MR fingerprinting and ADC maps. Linear mixed models compared two-reader means of T1, T2, and ADC. Generalized estimating equations logistic regression analysis was used to evaluate both MR fingerprinting and ADC in differentiating NTZ, cancers and noncancers, clinically significant (Gleason score ≥ 7) cancers from clinically insignificant lesions (noncancers and Gleason 6 cancers), and characterizing PI-RADS version 2 category 3 lesions.ResultsIn 67 men (mean age, 66 years ± 8 [standard deviation]) with 75 lesions, targeted biopsy revealed 37 cancers (six PI-RADS category 3 cancers and 31 PI-RADS category 4 or 5 cancers) and 38 noncancers (31 PI-RADS category 3 lesions and seven PI-RADS category 4 or 5 lesions). The T1, T2, and ADC of NTZ (1800 msec ± 150, 65 msec ± 22, and [1.13 ± 0.19] × 10-3 mm2/sec, respectively) were higher than those in cancers (1450 msec ± 110, 36 msec ± 11, and [0.57 ± 0.13] × 10-3 mm2/sec, respectively; P < .001 for all). The T1, T2, and ADC in cancers were lower than those in noncancers (1620 msec ± 120, 47 msec ± 16, and [0.82 ± 0.13] × 10-3 mm2/sec, respectively; P = .001 for T1 and ADC and P = .03 for T2). The area under the receiver operating characteristic curve (AUC) for T1 plus ADC was 0.94 for separation. T1 and ADC in clinically significant cancers (1440 msec ± 140 and [0.58 ± 0.14] × 10-3 mm2/sec, respectively) were lower than those in clinically insignificant lesions (1580 msec ± 120 and [0.75 ± 0.17] × 10-3 mm2/sec, respectively; P = .001 for all). The AUC for T1 plus ADC was 0.81 for separation. Within PI-RADS category 3 lesions, T1 and ADC of cancers (1430 msec ± 220 and [0.60 ± 0.17] × 10-3 mm2/sec, respectively) were lower than those of noncancers (1630 msec ± 120 and [0.81 ± 0.13] × 10-3 mm2/sec, respectively; P = .006 for T1 and P = .004 for ADC). The AUC for T1 was 0.79 for differentiating category 3 lesions.ConclusionMR fingerprinting-based relaxometry combined with apparent diffusion coefficient mapping may improve transition zone lesion characterization.© RSNA, 2019Online supplemental material is available for this article.

Accelerated Segmented Diffusion-Weighted Prostate Imaging for Higher Resolution, Higher Geometric Fidelity, and Multi-b Perfusion Estimation.

The aim of this study was to improve the geometric fidelity and spatial resolution of multi-b diffusion-weighted magnetic resonance imaging of the prostate. An accelerated segmented diffusion imaging sequence was developed and evaluated in 25 patients undergoing multiparametric magnetic resonance imaging examinations of the prostate. A reduced field of view was acquired using an endorectal coil. The number of sampled diffusion weightings, or b-factors, was increased to allow estimation of tissue perfusion based on the intravoxel incoherent motion (IVIM) model. Apparent diffusion coefficients measured with the proposed segmented method were compared with those obtained with conventional single-shot echo-planar imaging (EPI). Compared with single-shot EPI, the segmented method resulted in faster acquisition with 2-fold improvement in spatial resolution and a greater than 3-fold improvement in geometric fidelity. Apparent diffusion coefficient values measured with the novel sequence demonstrated excellent agreement with those obtained from the conventional scan (R = 0.91 for bmax = 500 s/mm and R = 0.89 for bmax = 1400 s/mm). The IVIM perfusion fraction was 4.0% ± 2.7% for normal peripheral zone, 6.6% ± 3.6% for normal transition zone, and 4.4% ± 2.9% for suspected tumor lesions. The proposed accelerated segmented prostate diffusion imaging sequence achieved improvements in both spatial resolution and geometric fidelity, along with concurrent quantification of IVIM perfusion.

Absence of thermal influence from the African Superswell and cratonic keels on the mantle transition zone beneath southern Africa: Evidence from receiver function imaging

The depths of the 410 km (d410) and 660 km (d660) discontinuities beneath southern Africa, which is presumably underlain by the lower-mantle African Superswell, are imaged in 1∘ radius consecutive circular bins using over 6400 P-to-S receiver functions (RFs) recorded by 130 seismic stations over a 27 yr period. When the IASP91 standard Earth model is utilized for moveout correction and time-depth conversion, a normal mantle transition zone (MTZ) thickness of 246 ± 7 km is observed, suggesting that the Superswell has no discernible effect on mantle transition zone temperature. Based on the negligible disparity of the mean MTZ thicknesses between on (246 ± 6 km) and off (246 ± 8 km) cratonic regions, we conclude that the deep Archean cratonic keels possess limited influence on MTZ thermal structure. The apparently shallower-than-normal MTZ discontinuities and the parallelism between the d410 and d660 are mostly the results of upper mantle high wave speed anomalies probably corresponding to a thick lithosphere with a mean thickness of about 245 km beneath the Kaapvaal and 215 km beneath the Zimbabwe cratons. In contradiction to conclusions from some of the previous studies, the resulting spatial distribution of the stacking amplitudes of the P-to-S converted phases at the discontinuities is inconsistent with the presence of an excessive amount of water in the MTZ and atop the d410.

Phosphatidylinositol 4,5-bisphosphate regulates cilium transition zone maturation in Drosophila melanogaster.

Cilia are cellular antennae that are essential for human development and physiology. A large number of genetic disorders linked to cilium dysfunction are associated with proteins that localize to the ciliary transition zone (TZ), a structure at the base of cilia that regulates trafficking in and out of the cilium. Despite substantial effort to identify TZ proteins and their roles in cilium assembly and function, processes underlying maturation of TZs are not well understood. Here, we report a role for the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) in TZ maturation in the Drosophila melanogaster male germline. We show that reduction of cellular PIP2 levels through ectopic expression of a phosphoinositide phosphatase or mutation of the type I phosphatidylinositol phosphate kinase Skittles induces formation of longer than normal TZs. These hyperelongated TZs exhibit functional defects, including loss of plasma membrane tethering. We also report that the onion rings (onr) allele of DrosophilaExo84 decouples TZ hyperelongation from loss of cilium-plasma membrane tethering. Our results reveal a requirement for PIP2 in supporting ciliogenesis by promoting proper TZ maturation.

Quantification of Total and Intracellular Sodium Concentration in Primary Prostate Cancer and Adjacent Normal Prostate Tissue With Magnetic Resonance Imaging.

The aim of this study was to measure the tissue sodium concentration (TSC) within tumors and normal prostate in prostate cancer patients, using prostatectomy as pathological criterion standard. Fifteen patients with biopsy-proven, magnetic resonance imaging (MRI) visible, intermediate- or high-risk prostate cancer underwent a dedicated research sodium MRI, before treatment with radical prostatectomy. All participants signed written informed consent for this institutional review board-approved prospective study. 3 T MRI acquired using a dedicated multinuclear clamshell transmit coil and a bespoke dual-tuned H/Na endorectal receive coil, with intracellular-sodium imaging acquired using inversion recovery sequences; a phantom-based calibration enabled quantitative sodium maps. Regions of interest were defined for normal peripheral zone (PZ) and transition zone (TZ) and tumor regions, referenced from histopathology maps. A 1-way analysis of variance compared normal and tumor tissue, using Tukey test for multiple comparisons. Two patients were excluded due to artifact; software error resulted in 1 further intracellular-sodium failure. Fifteen tumors were detected (13 PZ, 2 TZ) in 13 patients: Gleason 3 + 3 (n = 1), 3 + 4 (6), 3 + 5 (2), 4 + 3 (5), 4 + 5 (1). Both mean TSC and intracellular-sodium were significantly higher in normal PZ (39.2 and 17.5 mmol/L, respectively) versus normal TZ (32.9 and 14.7; P < 0.001 and P = 0.02). Mean TSC in PZ tumor (45.0 mmol/L) was significantly higher than both normal PZ and TZ tissue (P < 0.001). Intracellular sodium in PZ tumors (19.9 mmol/L) was significantly higher than normal TZ (P < 0.001) but not normal PZ (P = 0.05). Mean TSC and intracellular-sodium was lower in Gleason ≤3 + 4 tumors (44.4 and 19.5 mmol/L, respectively) versus ≥4 + 3 (45.6 and 20.2), but this was not significant (P = 0.19 and P = 0.29). Tissue sodium concentration and intracellular sodium concentrations of prostate tumors were quantified, with PZ tumors demonstrating a significantly increased TSC.

MP11-03 PRIMARY TUMOR RESPONSE TO NEXT GENERATION ANTI-ANDROGEN THERAPY ASSESSED BY PRE-POST TREATMENT MRI PRIOR TO RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II1 Apr 2018MP11-03 PRIMARY TUMOR RESPONSE TO NEXT GENERATION ANTI-ANDROGEN THERAPY ASSESSED BY PRE-POST TREATMENT MRI PRIOR TO RADICAL PROSTATECTOMY Chad A. Reichard, Tharakeswala K. Bathala, Justin R. Gregg, Mary Achim, Janet Kukreja, Eleni Efstathiou, John W. Davis, and Brian F. Chapin Chad A. ReichardChad A. Reichard More articles by this author , Tharakeswala K. BathalaTharakeswala K. Bathala More articles by this author , Justin R. GreggJustin R. Gregg More articles by this author , Mary AchimMary Achim More articles by this author , Janet KukrejaJanet Kukreja More articles by this author , Eleni EfstathiouEleni Efstathiou More articles by this author , John W. DavisJohn W. Davis More articles by this author , and Brian F. ChapinBrian F. Chapin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.369AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pre-treatment predictors of local therapy benefit in advanced prostate cancer (aPCa) are of interest. We aimed to describe differences in diffusion weighted imaging characteristics after treatment with ADT and examine whether these changes were associated with pT stage post radical prostatectomy (RP). METHODS 42 pts with aPCa treated with pre-surgical ADT from 2011-2017 were reviewed (16 pts treated with abi+enza, 7 pts treated with abi+LHRH agonist, and 19 pts treated with LHRH agonist/antagonist alone). All pts had 1.5T MRI with endorectal coil pre-ADT initiation and then had repeat MRI prior to RP. Dominant lesion mapped on RP pathology report was correlated to the lesion seen on MR, and ADC (apparent diffusion coefficient) values of the tumor and benign tissue were recorded. We compared pre-post ADC values in tumor, normal prostate tissue and examined for association of changes in imaging parameters and pT stage. RESULTS Median PSA was (16.8 IQR 9.2-28.1) and pt characteristics are summarized in table. Mean tumor ADC was larger after ADT treatment 1111+/-233 (10-6mm2/sec) vs prior to ADT 800+/-120 (10-6mm2/sec) p<.01. Mean ADC of normal transition zone and normal peripheral zone were both decreased post ADT (1363+/-160 to 1222+/-171 and 1612+/-256 to 1511+/-215, both p<.01). Mean largest tumor cross sectional area was decreased after ADT (3.31+/-3.01 cm2 to 1.44+/-1.21 cm2, p<.01). Mean prostate volume was also decreased after ADT (49.4+/-24.9 cm3 to 25.3+/-15.9cm3, p<.01). The mean post ADT increase in tumor ADC was 32% for patients treated LHRH agonist/antagonist alone compared to 53% for patients treated with abi +/- enza (p=0.039). There was no relation between relative tumor area post-treatment (p=0.34) or >50% change in ADC post-treatment (p=0.27) and >= pT3b disease. CONCLUSIONS This is the first report to our knowledge of prostate MRI prior to and after combination next generation anti-androgen treatment. Larger increases in post treatment ADC values were seen in patients treated with abi +/- enza compared to LHRH agonist/antagonist alone. While there was no association between changes in DWI imaging characteristics and worse pathologic outcome, further correlation with clinical outcomes may demonstrate imaging findings predictive of benefit from local therapy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e127-e128 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Chad A. Reichard More articles by this author Tharakeswala K. Bathala More articles by this author Justin R. Gregg More articles by this author Mary Achim More articles by this author Janet Kukreja More articles by this author Eleni Efstathiou More articles by this author John W. Davis More articles by this author Brian F. Chapin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population

ObjectiveTo evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population.MethodsThirty-patients were imaged at 3 T including DKI (Kapp and Dapp) with b-values 150/450/800/1150/1500 s/mm2 and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics.ResultsTwenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and Dapp were significantly lower and the Kapp and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and Dapp and higher Kapp and MTR compared to normal PZ. MTR showed a moderate correlation to Kapp (r = 0.570) and Dapp (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825).ConclusionADC, Dapp, Kapp and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease.Key Points• MTR was significantly higher in PZ and TZ tumours versus normal tissue• Kappwas significantly lower and Dapphigher for PZ and TZ tumours• There was no incremental value for DKI/MTI over mono-exponential ADC parameters• No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease• Divergent MTR/DKI values in TZ tumours suggests they offer different functional information

Serotonin regulates prostate growth through androgen receptor modulation

Aging and testosterone almost inexorably cause benign prostatic hyperplasia (BPH) in Human males. However, etiology of BPH is largely unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and presents in high concentration in normal prostatic transition zone, but its function in prostate physiology is unknown. Previous evidence demonstrated that neuroendocrine cells and 5-HT are decreased in BPH compared to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth. In vitro, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). This 5-HT’s inhibitory mechanism is also present in human cells of normal prostate and BPH, namely in cell lines expressing AR when treated with testosterone. In both models, 5-HT’s inhibitory mechanism was replicated by specific agonists of 5-Htr1a and 5-Htr1b. Since peripheral 5-HT production is specifically regulated by tryptophan hydroxylase 1(Tph1), we showed that Tph1 knockout mice present higher prostate mass and up-regulation of AR when compared to wild-type, whereas 5-HT treatment restored the prostate weight and AR levels. As 5-HT is decreased in BPH, we present here evidence that links 5-HT depletion to BPH etiology through modulation of AR. Serotoninergic prostate pathway should be explored as a new therapeutic target for BPH.

Evaluation of fitting models for prostate tissue characterization using extended-range b-factor diffusion-weighted imaging.

To compare the fitting and tissue discrimination performance of biexponential, kurtosis, stretched exponential, and gamma distribution models for high b-factor diffusion-weighted images in prostate cancer. Diffusion-weighted images with 15 b-factors ranging from b = 0 to 3500 s/mm2 were obtained in 62 prostate cancer patients. Pixel-wise signal decay fits for each model were evaluated with the Akaike Information Criterion (AIC). Parameter values for each model were determined within normal prostate and the index lesion. Their potential to differentiate normal from cancerous tissue was investigated through receiver operating characteristic analysis and comparison with Gleason score. The biexponential slow diffusion fraction fslow , the apparent kurtosis diffusion coefficient ADCK , and the excess kurtosis factor K differ significantly among normal peripheral zone (PZ), normal transition zone (TZ), tumor PZ, and tumor TZ. Biexponential and gamma distribution models result in the lowest AIC, indicating a superior fit. Maximum areas under the curve (AUCs) of all models ranged from 0.93 to 0.96 for the PZ and from 0.95 to 0.97 for the TZ. Similar AUCs also result from the apparent diffusion coefficient (ADC) of a monoexponential fit to a b-factor sub-range up to 1250 s/mm2 . For kurtosis and stretched exponential models, single parameters yield the highest AUCs, whereas for the biexponential and gamma distribution models, linear combinations of parameters produce the highest AUCs. Parameters with high AUC show a trend in differentiating low from high Gleason score, whereas parameters with low AUC show no such ability. All models, including a monoexponential fit to a lower-b sub-range, achieve similar AUCs for discrimination of normal and cancer tissue. The biexponential model, which is favored statistically, also appears to provide insight into disease-related microstructural changes. Magn Reson Med 79:2346-2358, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer.

To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. • Machine-based analysis of MR radiomics outperformed in TZ cancer against PI-RADS. • Adding MR radiomics significantly improved the performance of PI-RADS. • DKI-derived Dapp and Kapp were two strong markers for the diagnosis of PCa.