Kristin K. Porter

Comparative analysis of cortical layering and supragranular layer enlargement in rodent carnivore and primate species

The mammalian cerebral cortex is composed of individual layers characterized by the cell types they contain and their afferent and efferent connections. The current study examined the raw, and size-normalized, laminar thicknesses in three cortical regions (somatosensory, motor, and premotor) of fourteen species from three orders of mammals: primates, carnivores, and rodents. The proportional size of the pyramidal cell layers (supra- and infragranular) varied between orders but was similar within orders despite wide variance in absolute cortical thickness. Further, supragranular layer thickness was largest in primates (46 +/- 3 percent), followed by carnivores (36 +/- 3 percent), and then rodents (19 +/- 4 percent), suggesting a distinct difference in the proportion of cortex devoted to corticocortical connectivity across these orders. Although measures of supragranular layer thickness are highly correlated with measures of overall brain size, such associations are not present when independent contrasts are used to control for phylogenetic inertia. Interestingly, neurogenesis time span remains strongly associated with supragranular layer thickness despite size normalization and controlling for phylogenetic inertia. Such layering differences between orders, and similarities amongst species within an order, suggest that supragranular layer expansion may have occurred early in mammalian evolution and may be related to ontogenetic variables such as neurogenesis time span rather than measures of overall size.

Effects of Reward and Behavioral Context on Neural Activity in the Primate Inferior Colliculus

Neural activity in the inferior colliculus (IC) likely plays an integral role in the processing of various auditory parameters, such as sound location and frequency. However, little is known about the extent to which IC neural activity may be influenced by the context in which sounds are presented. In this study, we examined neural activity of IC neurons in the rhesus monkey during an auditory task in which a sound served as a localization target for a saccade. Correct performance was rewarded, and the magnitude of the reward was varied in some experiments. Neural activity was also assessed during a task in which the monkey maintained fixation of a light while ignoring the sound, as well as when sounds were presented in the absence of any task. We report that neural activity increased late in the trial in the saccade task in 58% of neurons and that the level of activity throughout the trials could be modulated by reward magnitude for many neurons. The late-trial neural activity similarly increased in the fixation task in 39% of the neurons tested for this task but was not observed when sounds were presented in the absence of a behavioral task and reward. Together, these results suggest that a reward-related signal influences neural activity in the IC.

Visual- and saccade-related signals in the primate inferior colliculus.

The inferior colliculus (IC) is normally thought of as a predominantly auditory structure because of its early position in the ascending auditory pathway just before the auditory thalamus. Here, we show that a majority of IC neurons (64% of 180 neurons) in awake monkeys carry visual- and/or saccade-related signals in addition to their auditory responses (P < 0.05). The response patterns involve primarily excitatory visual responses, but also increased activity time-locked to the saccade, slow rises in activity time-locked to the onset of the visual stimulus, and inhibitory responses. The presence of these visual-related signals suggests that the IC plays a role in integrating visual and auditory information. More broadly, our results show that interactions between sensory pathways can occur at very early points in sensory processing streams, which implies that multisensory integration may be a low-level rather than an exclusively high-level process.

MRI/US fusion-guided prostate biopsy allows for equivalent cancer detection with significantly fewer needle cores in biopsy-naive men

PURPOSE We aimed to investigate the efficiency and cancer detection of magnetic resonance imaging (MRI) / ultrasonography (US) fusion-guided prostate biopsy in a cohort of biopsy-naive men compared with standard-of-care systematic extended sextant transrectal ultrasonography (TRUS)-guided biopsy. METHODS From 2014 to 2016, 72 biopsy-naive men referred for initial prostate cancer evaluation who underwent MRI of the prostate were prospectively evaluated. Retrospective review was performed on 69 patients with lesions suspicious for malignancy who underwent MRI/US fusion-guided biopsy in addition to systematic extended sextant biopsy. Biometric, imaging, and pathology data from both the MRI-targeted biopsies and systematic biopsies were analyzed and compared. RESULTS There were no significant differences in overall prostate cancer detection when comparing MRI-targeted biopsies to standard systematic biopsies (P = 0.39). Furthermore, there were no significant differences in the distribution of severity of cancers based on grade groups in cases with cancer detection (P = 0.68). However, significantly fewer needle cores were taken during the MRI/US fusion-guided biopsy compared with systematic biopsy (63% less cores sampled, P < 0.001) CONCLUSION: In biopsy-naive men, MRI/US fusion-guided prostate biopsy offers equal prostate cancer detection compared with systematic TRUS-guided biopsy with significantly fewer tissue cores using the targeted technique. This approach can potentially reduce morbidity in the future if used instead of systematic biopsy without sacrificing the ability to detect prostate cancer, particularly in cases with higher grade disease.

Contrast-enhanced ultrasound of benign liver lesions

Liver lesions are often incidentally detected on ultrasound examination and may be incompletely characterized, requiring further imaging. Contrast-enhanced ultrasound (CEUS) was recently approved by the Food and Drug Administration in the United States for liver lesion characterization. CEUS has the ability to characterize focal liver lesions and has been shown to be superior to color Doppler and power Doppler ultrasound in the detection of tumor vascularity. Differentiating benign from malignant liver lesions is essential to characterizing liver lesions. The CEUS imaging characteristics of benign liver lesions are reviewed, including hepatic cysts, hemangiomas, focal fat, focal nodular hyperplasia, hepatocellular adenomas, abscesses, and traumatic lesions.

Defining the optimal method for reporting prostate cancer grade and tumor extent on magnetic resonance/ultrasound fusion–targeted biopsies

Magnetic resonance (MR)/ultrasound fusion-targeted biopsy (TB) routinely samples multiple cores from each MR lesion of interest. Pathologists can evaluate the extent of cancer involvement and grade using an individual core (IC) or aggregate (AG) method, which could potentially lead to differences in reporting. We reviewed patients who underwent TB followed by radical prostatectomy (RP). TB cores were evaluated for grade and tumor extent by 2 methods. In the IC method, the grade for each TB lesion was based on the core with the highest Gleason score. Tumor extent for each TB was based on the core with the highest percent of tumor involvement. In the AG method, the tumor from all cores within each TB lesion was aggregated to determine the final composite grade and percentage of tumor involvement. Each method was compared with MR lesional volume, MR lesional density (lesion volume/prostate volume), and RP. Fifty-five patients underwent TB followed by RP. Extent of tumor by the AG method showed a better correlation with target lesion volume (r= 0.27,P= .022) and lesional density (r = 0.32, P = .008) than did the IC method (r= 0.19 [P = .103] andr= 0.22 [P = .062]), respectively. Extent of tumor on TB was associated with extraprostatic extension on RP by the AG method (P= .04), but not by the IC method. This association was significantly higher in patients with a grade group (GG) of 3 or higher (P= .03). A change in cancer grade occurred in 3 patients when comparing methods (2 downgraded GG3 to GG2, 1 downgraded GG4 to GG3 by the AG method). For multiple cores obtained via TB, the AG method better correlates with target lesion volume, lesional density, and extraprostatic extension.

Prostate Cancer Imaging and Biomarkers Guiding Safe Selection of Active Surveillance

Background Active surveillance (AS) is a widely adopted strategy to monitor men with low-risk, localized prostate cancer (PCa). Current AS inclusion criteria may misclassify as many as one in four patients. The advent of multiparametric magnetic resonance imaging (mpMRI) and novel PCa biomarkers may offer improved risk stratification. We performed a review of recently published literature to characterize emerging evidence in support of these novel modalities. Methods An English literature search was conducted on PubMed for available original investigations on localized PCa, AS, imaging, and biomarkers published within the past 3 years. Our Boolean criteria included the following terms: PCa, AS, imaging, biomarker, genetic, genomic, prospective, retrospective, and comparative. The bibliographies and diagnostic modalities of the identified studies were used to expand our search. Results Our review identified 222 original studies. Our expanded search yielded 244 studies. Among these, 70 met our inclusion criteria. Evidence suggests mpMRI offers improved detection of clinically significant PCa, and MRI-fusion technology enhances the sensitivity of surveillance biopsies. Multiple studies demonstrate the promise of commercially available screening assays for prediction of AS failure, and several novel biomarkers show promise in this setting. Conclusion In the era of AS for men with low-risk PCa, improved strategies for proper stratification are needed. mpMRI has dramatically enhanced the detection of clinically significant PCa. The advent of novel biomarkers for prediction of aggressive disease and AS failure has shown some initial promise, but further validation is warranted.

Detection of extraprostatic disease and seminal vesicle invasion in patients undergoing magnetic resonance imaging-targeted prostate biopsies

Background Finding incidental extraprostatic extension (EPE) or seminal vesicle invasion (SVI) by prostate cancer (PCa) is rare on standard prostate biopsy. We evaluated the clinical-pathologic features associated with EPE and SVI on multiparametric magnetic resonance imaging (MRI)/ultrasound (US) fusion-guided targeted biopsy (TB). Methods A retrospective review was performed from 2014–2017, selecting patients who had undergone TB. Clinical, pathologic, and radiologic features were evaluated. Results Five out of 333 (1.5%) patients who had PCa detected on TB had EPE and/or SVI. The average age and prostate-specific antigen (PSA) was 71 years and 17 ng/mL, respectively. The average number of cores taken on TB was 4.2. Two patients had a prior negative SB and two patients had a prior positive SB, one of which underwent radiation therapy. All patients had a PIRADSv2 suspicion score of 4 or 5. Four out of five (80%) patients underwent both SB and concurrent TB, of which 3/4 (75%) had EPE identified only on TB. One out of four (25%) patients also had both EPE and SVI, identified only on TB. One patient underwent only TB for MRI suspicion of SVI, which was pathologically confirmed on TB. On TB, one patient had Grade Group 3, two patients had Grade Group 4, and two patients had Grade Group 5 PCa. Perineural invasion (PNI) was present in 4/5 (80%) patients on TB. Conclusions Based on our small series, we hypothesize that MRI/US fusion TB outperforms SB in the identification of EPE and SVI. However, given the small sample size and the overall rarity of these pathologic findings on prostate biopsy, further validation is needed.

MRI findings guiding selection of active surveillance for prostate cancer: a review of emerging evidence

Active surveillance (AS) for prostate cancer (PCa) is generally considered to be a safe strategy for men with low-risk, localized disease. However, as many as 1 in 4 patients may be incorrectly classified as AS-eligible using traditional inclusion criteria. The use of multiparametric magnetic resonance imaging (mpMRI) may offer improved risk stratification in both the initial diagnostic and disease monitoring setting. We performed a review of recently published studies to evaluate the utility of this imaging modality for this clinical setting. An English literature search was conducted on PubMed for original investigations on localized PCa, AS, and magnetic resonance imaging. Our Boolean criteria included the following terms: PCa, AS, imaging, MRI, mpMRI, prospective, retrospective, and comparative. Our search excluded publication types such as comments, editorials, guidelines, reviews, or interviews. Our literature review identified 71 original investigations. Among these, 52 met our inclusion criteria. Evidence suggests mpMRI improves characterization of clinically significant prostate cancer (csPCa) foci, and the enhanced detection and risk-stratification afforded by this modality may keep men from being inappropriately placed on AS. Use of serial mpMRI may also permit longer intervals between confirmatory biopsies. Multiple studies demonstrate the benefit of MRI-targeted biopsies. The use of mpMRI of the prostate offers improved confidence in risk-stratification for men with clinically low-risk PCa considering AS. While on AS, serial mpMRI and MRI-targeted biopsy aid in the detection of aggressive disease transformation or foci of clinically-significant cancer undetected on prior biopsy sessions.

Role of Prostate MRI in the Setting of Active Surveillance for Prostate Cancer

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