Deep-learning-based reconstruction of T2-weighted magnetic resonance imaging of the prostate accelerated by compressed sensing provides improved image quality at half the acquisition time.

Background: Deep-learning-based reconstruction (DLR) improves the quality of magnetic resonance (MR) images which allows faster acquisitions. The aim of this study was to compare the image quality of standard and accelerated T2 weighted turbo-spin-echo (TSE) images of the prostate reconstructed with and without DLR and to find associations between perceived image quality and calculated image characteristics. Methods: In a cohort of 47 prospectively enrolled consecutive patients referred for bi-parametric prostate magnetic resonance imaging (MRI), two T2-TSE acquisitions in the transverse plane were acquired on a 3T scanner-a standard T2-TSE sequence and a short sequence accelerated by a factor of two using compressed sensing (CS). The images were reconstructed with and without DLR in super-resolution mode. The image quality was rated in six domains. Signal-to-noise ratio (SNR), and image sharpness were measured. Results: The mean acquisition time was 281±23 s for the standard and 140±12 s for the short acquisition (P<0.0001). DLR images had higher sharpness compared to non-DLR (P<0.001). Short and short-DLR had lower SNR than the standard and standard-DLR (P<0.001). The perceived image quality of short-DLR was rated better in all categories compared to the standard sequence (P<0.001 to P=0.004). All domains of subjective evaluation were correlated with measured image sharpness (P<0.001). Conclusions: T2-TSE acquisition of the prostate accelerated using CS combined with DLR reconstruction provides images with increased sharpness that have a superior quality as perceived by human readers compared to standard T2-TSE. The perceived image quality is correlated with measured image contrast.

Quantification and significance of extraprostatic findings on prostate MRI: a retrospective analysis and three-tier classification.

OBJECTIVES: To quantify extraprostatic findings (EPFs) on prostate MRI, estimate the proportion of reported and unreported EPFs, assess their clinical importance, and propose standardized reporting of EPFs. MATERIALS AND METHODS: Prostate 3-T MRI studies, reports, and clinical data from 623 patients (age 67.9 ± 8.2 years) were retrospectively analyzed and re-evaluated for the presence of EPFs and their clinical significance: E1-no finding or findings that have no clinical significance; E2-potentially significant findings; and E3-significant findings. RESULTS: Secondary reading identified 1236 EPFs in 593 patients (1.98 ± 1.13 EPFs per patient, no EPFs in 30 patients), from which 468 (37.8%) were mentioned in the original report. The most common findings included diverticulosis (44% of patients), hydrocele (34%), inguinal fat hernia (16%), and bladder wall trabecular hypertrophy (15%). There were 80 (6.5%) E2 EPFs and 30 (2.4%) E3 EPFs. From E3 EPFs, 10 (33%) were not originally reported. A workup was suggested in 35 (52%) of the 67 originally reported E2 and E3 findings with follow-up and performed in 20 (30%). Fourteen (21%) EPFs in 11 patients influenced their management. Four experienced radiologists originally reported 1.8 to 2.5 findings per patient (p < 0.0001). CONCLUSIONS: EPFs on prostate MRI are frequent, but only 2.4% are clinically significant (E3), and 33% of these are not reported. Only 30% of E2 and E3 findings are further explored, and 21% influence patient management. We suggest that an "E" category should be attached to the PI-RADS system to identify the presence of EPFs that require further workup. CRITICAL RELEVANCE STATEMENT: Extraprostatic findings on prostate MRI are frequent, but only 2.4% are clinically significant (E3), and 33% of these are not reported. We advocate standardized reporting of extraprostatic findings indicating their clinical significance. KEY POINTS: • Extraprostatic findings on prostate MRI are frequent with an average of two findings per patient. • 2.4% of extraprostatic findings are significant, and 33% of these are not reported. • There is a significant variability among experienced radiologists in reporting extraprostatic findings.

Coronary artery disease prediction based on breast arterial calcification in women undergoing mammography as a screening for breast cancer.

OBJECTIVE: The aim of the study was to test the potential role of breast arterial calcification (BAC) in the prediction of coronary artery disease (CAD) in women. The criterion standard for CAD diagnostics was coronary angiography. METHODS: This retrospective study enrolled 163 consecutive women, who underwent digital mammography and coronary angiography in our hospital. We assessed the presence and severity of BAC, and tested whether the presence and/or extent of BAC could be a predictor for CAD, quantified by Gensini score. RESULTS: BAC was presented in 34 patients (21%). Neither the presence of CAD (17 patients, 50%, vs 55 42.6%, P = 0.44), nor the Gensini score (20.5 ±â€Š29.7 vs 15.4 ±â€Š24.1, P = 0.3) differed significantly between BAC-present and BAC-absent patients.A finding of triple-vessel disease, however, more frequently occurred in the BAC-present (seven patients, 20.6%) than in the BAC-absent (nine patients, 7%) group, odds ratio (OR) 3.1, 95% CI 1-9.5, P = 0.049. The presence of BAC did not significantly increase the odds for the presence of CAD (OR = 1.29, P = 0.54). Among the subgroup of patients with CAD, BAC presence was associated with triple vessel disease (OR = 3.34, P = 0.049). CONCLUSIONS: We did not confirm BAC as a predictor of CAD. However, BAC showed association with more severe forms of coronary atherosclerosis (triple vessel disease).

Video Summary:http://links.lww.com/MENO/A728 .

Early ear neuronal development, but not olfactory or lens development, can proceed without SOX2.

SOX2 is essential for maintaining neurosensory stem cell properties, although its involvement in the early neurosensory development of cranial placodes remains unclear. To address this, we used Foxg1-Cre to conditionally delete Sox2 during eye, ear, and olfactory placode development. Foxg1-Cre mediated early deletion of Sox2 eradicates all olfactory placode development, and disrupts retinal development and invagination of the lens placode. In contrast to the lens and olfactory placodes, the ear placode invaginates and delaminates NEUROD1 positive neurons. Furthermore, we show that SOX2 is not necessary for early ear neurogenesis, since the early inner ear ganglion is formed with near normal central projections to the hindbrain and peripheral projections to the undifferentiated sensory epithelia of E11.5-12.5 ears. However, later stages of ear neurosensory development, in particular, the late forming auditory system, critically depend on the presence of SOX2. Our data establish distinct differences for SOX2 requirements among placodal sensory organs with similarities between olfactory and lens but not ear placode development, consistent with the unique neurosensory development and molecular properties of the ear.

The role of palliative care in acute care setting.

While terminal palliative care focuses primarily on the management of symptoms of immediate dying, early palliative care provides an opportunity for the patient and his loved ones to understand the trajectory of the illness, to receive support for coping with the diagnosis, increase the quality of decision-making to match the patients values and preferences. The emphasis is on realistic expectations of the outcome of treatment and timely anticipation of further disease course. The paper focuses on an overview of the evidence of palliative and supportive interventions, comparing the different trigger mechanisms for palliative intervention and presents the content of the intervention of the palliative team. The establishment and integration of the consultative palliative team in the tertiary hospital is described. An illustrative care report describes the goals of care conversation and its impact on advance care planning. Palliative care is widely accepted and recommended standard of high quality care for seriously ill patients. In the Czech Republic, it is necessary to extend its availability for patients hospitalized in acute care setting.

Characteristic CT features of pheochromocytomas - probability model calculation tool based on a multicentric study.

OBJECTIVES: The aim of the study was to evaluate the CT features of adrenal tumors in an effort to identify features specific to pheochromocytomas and second, to define a feasible probability calculation model. METHODS: This multicentric retrospective study included patients from the period 2003 to 2017 with an appropriate CT examination and a histological diagnosis of an adrenal adenoma, pheochromocytoma, adrenocortical carcinoma, or metastasis. In total, 346 patients were suitable for the CT image analysis, which included evaluation of the largest diameter, the shape of the lesion, the presence of central necrosis and its margins, and the presence of an enhancing peripheral rim ("ring sign"). RESULTS: Pheochromocytomas have a significantly more spherical shape (P<0.001), whereas an elliptical shape significantly reduces the probability of a pheochromocytoma (odds ratio = 0.015), as does another shape (odds ratio = 0.006). A "ring sign" is also more frequent in pheochromocytomas compared to other adrenal tumors (P=0.001, odds ratio = 6.49). A sharp necrosis also increases the probability of a pheochromocytoma more than unsharp necrosis (odds ratio 231.6 vs. 20.2). The probability calculation model created on the basis of the results confirms a high sensitivity and specificity (80% and 95%). CONCLUSION: This study confirms the value of anatomical features in the assessment of adrenal masses with the ability to significantly improve the identification of pheochromocytomas. Advanced assessment of the tumor shape was defined and a original comprehensive calculating tool of the pheochromocytoma probability was created on the basis of the results presented here and could be used in clinical routine.

A computer-assisted system for handheld whole-breast ultrasonography.

PURPOSE: Breast ultrasonography (US) presents an alternative to mammography in young asymptomatic individuals and a complementary examination in screening of women with dense breasts. Handheld US is the standard-of-care, yet when used in whole-breast examination, no effort has been devoted to monitoring breast coverage and missed regions, which is the purpose of this study. METHODS: We introduce a computer-aided system assisting radiologists and US technologists in covering the whole breast with minimum alteration to the standard workflow. The proposed system comprises a standard US device, proprietary electromagnetic 3D tracking technology and software that combines US visual and tracking data to estimate a probe trajectory, total time spent in different breast segments, and a map of missed regions. A case study, which involved four radiologists (two junior and two senior) performing whole-breast ultrasound in 75 asymptomatic patients, was conducted to test the importance and relevance of the system. RESULTS: The mean process time per breast was [Formula: see text], with no statistically significant difference between the left and the right sides, and slightly longer examination time of junior radiologists. The process time density shows that central parts of the breast have better coverage compared to the periphery. Within the central part, missed regions of minimum detectable size of [Formula: see text] occur in [Formula: see text] of examinations, and non-negligible [Formula: see text] regions occur in [Formula: see text] of cases. CONCLUSION: The results of the case study indicate that missed regions are present in handheld whole-breast US, which renders the proposed system for tracking the probe position during examination a valuable tool for monitoring coverage.

Neurod1 Is Essential for the Primary Tonotopic Organization and Related Auditory Information Processing in the Midbrain.

Hearing depends on extracting frequency, intensity, and temporal properties from sound to generate an auditory map for acoustical signal processing. How physiology intersects with molecular specification to fine tune the developing properties of the auditory system that enable these aspects remains unclear. We made a novel conditional deletion model that eliminates the transcription factor NEUROD1 exclusively in the ear. These mice (both sexes) develop a truncated frequency range with no neuroanatomically recognizable mapping of spiral ganglion neurons onto distinct locations in the cochlea nor a cochleotopic map presenting topographically discrete projections to the cochlear nuclei. The disorganized primary cochleotopic map alters tuning properties of the inferior colliculus units, which display abnormal frequency, intensity, and temporal sound coding. At the behavioral level, animals show alterations in the acoustic startle response, consistent with altered neuroanatomical and physiological properties. We demonstrate that absence of the primary afferent topology during embryonic development leads to dysfunctional tonotopy of the auditory system. Such effects have never been investigated in other sensory systems because of the lack of comparable single gene mutation models.SIGNIFICANCE STATEMENT All sensory systems form a topographical map of neuronal projections from peripheral sensory organs to the brain. Neuronal projections in the auditory pathway are cochleotopically organized, providing a tonotopic map of sound frequencies. Primary sensory maps typically arise by molecular cues, requiring physiological refinements. Past work has demonstrated physiologic plasticity in many senses without ever molecularly undoing the specific mapping of an entire primary sensory projection. We genetically manipulated primary auditory neurons to generate a scrambled cochleotopic projection. Eliminating tonotopic representation to auditory nuclei demonstrates the inability of physiological processes to restore a tonotopic presentation of sound in the midbrain. Our data provide the first insights into the limits of physiology-mediated brainstem plasticity during the development of the auditory system.

Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation.

The programming of cell fate by transcription factors requires precise regulation of their time and level of expression. The LIM-homeodomain transcription factor Islet1 (Isl1) is involved in cell-fate specification of motor neurons, and it may play a similar role in the inner ear. In order to study its role in the regulation of vestibulo-motor development, we investigated a transgenic mouse expressing Isl1 under the Pax2 promoter control (Tg +/- ). The transgenic mice show altered level, time, and place of expression of Isl1 but are viable. However, Tg +/- mice exhibit hyperactivity, including circling behavior, and progressive age-related decline in hearing, which has been reported previously. Here, we describe the molecular and morphological changes in the cerebellum and vestibular system that may cause the hyperactivity of Tg +/- mice. The transgene altered the formation of folia in the cerebellum, the distribution of calretinin labeled unipolar brush cells, and reduced the size of the cerebellum, inferior colliculus, and saccule. Age-related progressive reduction of calbindin expression was detected in Purkinje cells in the transgenic cerebella. The hyperactivity of Tg +/- mice is reduced upon the administration of picrotoxin, a non-competitive channel blocker for the γ-aminobutyric acid (GABA) receptor chloride channels. This suggests that the overexpression of Isl1 significantly affects the functions of GABAergic neurons. We demonstrate that the overexpression of Isl1 affects the development and function of the cerebello-vestibular system, resulting in hyperactivity.

Incomplete and delayed Sox2 deletion defines residual ear neurosensory development and maintenance.

The role of Sox2 in neurosensory development is not yet fully understood. Using mice with conditional Islet1-cre mediated deletion of Sox2, we explored the function of Sox2 in neurosensory development in a model with limited cell type diversification, the inner ear. In Sox2 conditional mutants, neurons initially appear to form normally, whereas late- differentiating neurons of the cochlear apex never form. Variable numbers of hair cells differentiate in the utricle, saccule, and cochlear base but sensory epithelium formation is completely absent in the apex and all three cristae of the semicircular canal ampullae. Hair cells differentiate only in sensory epithelia known or proposed to have a lineage relationship of neurons and hair cells. All initially formed neurons lacking hair cell targets die by apoptosis days after they project toward non-existing epithelia. Therefore, late neuronal development depends directly on Sox2 for differentiation and on the survival of hair cells, possibly derived from common neurosensory precursors.

Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice.

The development, maturation, and maintenance of the inner ear are governed by temporal and spatial expression cascades of transcription factors that form a gene regulatory network. ISLET1 (ISL1) may be one of the major players in this cascade, and in order to study its role in the regulation of inner ear development, we produced a transgenic mouse overexpressing Isl1 under the Pax2 promoter. Pax2-regulated ISL1 overexpression increases the embryonic ISL1(+) domain and induces accelerated nerve fiber extension and branching in E12.5 embryos. Despite these gains in early development, the overexpression of ISL1 impairs the maintenance and function of hair cells of the organ of Corti. Mutant mice exhibit hyperactivity, circling behavior, and progressive age-related decline in hearing functions, which is reflected in reduced otoacoustic emissions (DPOAEs) followed by elevated hearing thresholds. The reduction of the amplitude of DPOAEs in transgenic mice was first detected at 1 month of age. By 6-9 months of age, DPOAEs completely disappeared, suggesting a functional inefficiency of outer hair cells (OHCs). The timing of DPOAE reduction coincides with the onset of the deterioration of cochlear efferent terminals. In contrast to these effects on efferents, we only found a moderate loss of OHCs and spiral ganglion neurons. For the first time, our results show that the genetic alteration of the medial olivocochlear (MOC) efferent system induces an early onset of age-related hearing loss. Thus, the neurodegeneration of the MOC system could be a contributing factor to the pathology of age-related hearing loss.

Preparation and application of anti-peptide antibodies for detection of orphan cytochromes P450.

OBJECTIVES: Cytochromes P450 (CYP) are monooxygenases, which metabolize mostly hydrophobic endogenous and exogenous compounds. CYPs without any clear connection to metabolism are called "orphans". Interestingly, these "orphan" CYPs are over-expressed in tumor tissues. Thus, the main aim of the paper is the development of antibodies for immunodetection of these CYPs as potential malignancy markers. METHODS: Unique sequences of CYP2S1 and 2W1 were selected and peptides synthesized. Chickens were immunized with peptides bound to hemocyanin (KLH). The antibodies were isolated from egg yolks and their reactivity was tested by ELISA. Antibodies were further affinity purified on immobilized peptides. Western blots containing CYP2S1 and 2W1 standards were developed with purified antibodies. RESULTS: Using unique peptide immunogens of CYP2S1 and 2W1 the antibodies were developed. As judged from ELISA all chickens produced specific antibodies against the respective peptides. Both affinity purified antibodies against CYP2S1 peptide recognized the CYP2S1 standard on Western blots, but only one of four anti-peptide antibodies against CYP2W1 reacted with CYP2W1 standard. The antibodies were used for the detection of CYPs in cancer cell lines and human tissues samples. Although both CYPs were frequently co-expressed in cancer cells, CYP2S1 was solely induced in the cell line BxPC3, while CYP2W1 was predominantly present in cell lines MCF7 and HeLa. Our data show that anti-peptide antibodies are an indispensable tool for detection of homologous CYPs. CONCLUSIONS: The anti-peptide antibodies successfully recognized CYP2S1 and 2W1 in the cancer cell lines and tissue samples.