Low-Intensity Pulsed Ultrasound Neuromodulation of a Rodent's Spinal Cord Suppresses Motor Evoked Potentials.

OBJECTIVE: Here we investigate the ability of low-intensity ultrasound (LIUS) applied to the spinal cord to modulate the transmission of motor signals. METHODS: Male adult Sprague-Dawley rats (n = 10, 250-300 g, 15 weeks old) were used in this study. Anesthesia was initially induced with 2% isoflurane carried by oxygen at 4 L/min via a nose cone. Cranial, upper extremity, and lower extremity electrodes were placed. A thoracic laminectomy was performed to expose the spinal cord at the T11 and T12 vertebral levels. A LIUS transducer was coupled to the exposed spinal cord, and motor evoked potentials (MEPs) were acquired each minute for either 5- or 10-minutes of sonication. Following the sonication period, the ultrasound was turned off and post-sonication MEPs were acquired for an additional 5 minutes. RESULTS: Hindlimb MEP amplitude significantly decreased during sonication in both the 5- (p < 0.001) and 10-min (p = 0.004) cohorts with a corresponding gradual recovery to baseline. Forelimb MEP amplitude did not demonstrate any statistically significant changes during sonication in either the 5- (p = 0.46) or 10-min (p = 0.80) trials. CONCLUSION: LIUS applied to the spinal cord suppresses MEP signals caudal to the site of sonication, with recovery of MEPs to baseline after sonication. SIGNIFICANCE: LIUS can suppress motor signals in the spinal cord and may be useful in treating movement disorders driven by excessive excitation of spinal neurons.

Ablation of apparent diffusion coefficient hyperintensity clusters in mesial temporal lobe epilepsy improves seizure outcomes after laser interstitial thermal therapy.

OBJECTIVE: Laser interstitial thermal therapy (LiTT) is a minimally invasive surgical procedure for intractable mesial temporal epilepsy (mTLE). LiTT is safe and effective, but seizure outcomes are highly variable due to patient variability, suboptimal targeting, and incomplete ablation of the epileptogenic zone. Apparent diffusion coefficient (ADC) is a magnetic resonance imaging (MRI) sequence that can identify potential epileptogenic foci in the mesial temporal lobe to improve ablation and seizure outcomes. The objective of this study was to investigate whether ablation of tissue clusters with high ADC values in the mesial temporal structures is associated with seizure outcome in mTLE after LiTT. METHODS: Twenty-seven patients with mTLE who underwent LiTT at our institution were analyzed. One-year seizure outcome was categorized as complete seizure freedom (International League Against Epilepsy [ILAE] Class I) and residual seizures (ILAE Class II-VI). Volumes of hippocampus and amygdala were segmented from the preoperative T1 MRI sequence. Spatially distinct hyperintensity clusters were identified in the preoperative ADC map. Proportion of cluster volume and number ablated were associated with seizure outcomes. RESULTS: The mean age at surgery was 37.5 years and the mean follow-up duration was 1.9 years. Proportions of hippocampal cluster volume (p = .013) and number (p = .03) ablated were significantly higher in patients with seizure freedom. For amygdala clusters, the proportion of cluster number ablated was significantly associated with seizure outcome (p = .026). In the combined amygdalohippocampal complex, ablation of amygdalohippocampal clusters reliably predicted seizure outcome by their volume ablated (area under the curve [AUC] = 0.7670, p = .02). SIGNIFICANCE: Seizure outcome after LiTT in patients with mTLE was associated significantly with the extent of cluster ablation in the amygdalohippocampal complex. The results suggest that preoperative ADC analysis may help identify high-yield pathological tissue clusters that represent epileptogenic foci. ADC-based cluster analysis can potentially assist ablation targeting and improve seizure outcome after LiTT in mTLE.

Porcine Model of Spinal Cord Injury: A Systematic Review.

Spinal cord injury (SCI) is a devastating disease with limited effective treatment options. Animal paradigms are vital for understanding the pathogenesis of SCI and testing potential therapeutics. The porcine model of SCI is increasingly favored because of its greater similarity to humans. However, its adoption is limited by the complexities of care and range of testing parameters. Researchers need to consider swine selection, injury method, post-operative care, rehabilitation, behavioral outcomes, and histology metrics. Therefore, we systematically reviewed full-text English-language articles to evaluate study characteristics used in developing a porcine model and summarize the interventions that have been tested using this paradigm. A total of 63 studies were included, with 33 examining SCI pathogenesis and 30 testing interventions. Studies had an average sample size of 15 pigs with an average weight of 26 kg, and most used female swine with injury to the thoracic cord. Injury was most commonly induced by weight drop with compression. The porcine model is amenable to testing various interventions, including mean arterial pressure augmentation (n = 7), electrical stimulation (n = 6), stem cell therapy (n = 5), hypothermia (n = 2), biomaterials (n = 2), gene therapy (n = 2), steroids (n = 1), and nanoparticles (n = 1). It is also notable for its clinical translatability and is emerging as a valuable pre-clinical study tool. This systematic review can serve as a guideline for researchers implementing and testing the porcine SCI model.

Applications of elastography in operative neurosurgery: A systematic review.

Elastography is an imaging technology capable of measuring tissue stiffness and consistency. The technology has achieved widespread use in the workup and management of diseases of the liver, breast, thyroid, and prostate. Although elastography is increasingly being applied in neurosurgery, it has not yet achieved widespread adoption and many clinicians remain unfamiliar with the technology. Therefore, we sought to summarize the range of applications and elastography modalities available for neurosurgery, report its effectiveness in comparison with conventional imaging methods, and offer recommendations. All full-text English-language manuscripts on the use of elastography for neurosurgical procedures were screened using the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science databases. Thirty-two studies were included with 990 patients, including 21 studies on intracranial tumors, 5 on hydrocephalus, 4 on epilepsy, 1 on spinal cord compression, and 1 on adolescent scoliosis. Twenty studies used ultrasound elastography (USE) whereas 12 used magnetic resonance elastography (MRE). MRE studies were mostly used in the preoperative setting for assessment of lesion stiffness, tumor-brain adherence, diagnostic workup, and operative planning. USE studies were performed intraoperatively to guide resection of lesions, determine residual microscopic abnormalities, assess the tumor-brain interface, and study mechanical properties of tumors. Elastography can assist with resection of brain tissue, detection of microscopic lesions, and workup of hydrocephalus, among other applications under investigation. Its sensitivity often exceeds that of conventional MRI and ultrasound for identifying abnormal tissue and lesion margins.

Vascular Myelopathy Secondary to Compression of the Artery of Adamkiewicz From an Intrathecal Catheter: A Technical Case Report.

BACKGROUND AND IMPORTANCE: Although catheter-related complications in intrathecal drug delivery systems are relatively common, vascular myelopathy secondary to occlusion of the artery of Adamkiewicz (AoA) from an abutting intrathecal catheter has not yet been reported. In this study, we present a case of this extremely rare presentation, which resolved after decompression of the artery. CLINICAL PRESENTATION: A 39-year-old woman presented with lower extremity weakness and paresthesia. She had a 20-year history of severe chronic back pain and stable sensory disturbances below T8 as sequelae of multiple injuries after a motor vehicle accident. Three years before presentation in our clinic, she underwent baclofen pump placement because of neuropathic pain refractory to oral medication. After pump placement, she gradually developed myelopathic symptoms and dysautonomia. All medications through the pump were discontinued, but her symptoms continued to progress. Workup included a spinal angiogram that showed that her intrathecal catheter was abutting the left side of the AoA at the T12 level. After interdisciplinary evaluation, it was believed that her clinical presentation was attributable to vascular compression, and she underwent surgical removal of the catheter. Three years later, her symptoms have improved and her neurological examination returned to baseline before the catheter placement. CONCLUSION: Meticulous, multidisciplinary neurological and radiological evaluations were essential to diagnose the compression of the AoA as the cause of this patient's myelopathy. Although exceedingly rare, direct compression of the AoA by an intrathecal catheter should be on the differential diagnosis when evaluating for causes of vascular myelopathy.

Multimodal interventions to optimize spinal cord perfusion in patients with acute traumatic spinal cord injuries: a systematic review.

OBJECTIVE: The authors systematically reviewed current evidence for the utility of mean arterial pressure (MAP), intraspinal pressure (ISP), and spinal cord perfusion pressure (SCPP) as predictors of outcomes after traumatic spinal cord injury (SCI). METHODS: PubMed, Cochrane Reviews Library, EMBASE, and Scopus databases were queried in December 2020. Two independent reviewers screened articles using Covidence software. Disagreements were resolved by a third reviewer. The inclusion criteria for articles were 1) available in English; 2) full text; 3) clinical studies on traumatic SCI interventions; 4) involved only human participants; and 5) focused on MAP, ISP, or SCPP. Exclusion criteria were 1) only available in non-English languages; 2) focused only on the brain; 3) described spinal diseases other than SCI; 4) interventions altering parameters other than MAP, ISP, or SCPP; and 5) animal studies. Studies were analyzed qualitatively and grouped into two categories: interventions increasing MAP or interventions decreasing ISP. The Scottish Intercollegiate Guidelines Network level of evidence was used to assess bias and the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate confidence in the anticipated effects of each outcome. RESULTS: A total of 2540 unique articles were identified, of which 72 proceeded to full-text review and 24 were included in analysis. One additional study was included retrospectively. Articles that went through full-text review were excluded if they were a review paper (n = 12), not a full article (n = 12), a duplicate paper (n = 9), not a human study (n = 3), not in English (n = 3), not pertaining to traumatic SCI (n = 3), an improper intervention (n = 3), without intervention (n = 2), and without analysis of intervention (n = 1). Although maintaining optimal MAP levels is the current recommendation for SCI management, the published literature supports maintenance of SCPP as a stronger indicator of favorable outcomes. Studies also suggest that laminectomy and durotomy may provide better outcomes than laminectomy alone, although higher-level studies are needed. Current evidence is inconclusive on the effectiveness of CSF drainage for reducing ISP. CONCLUSIONS: This review demonstrates the importance of assessing how different interventions may vary in their ability to optimize SCPP.

Apparent diffusion coefficient of piriform cortex and seizure outcome in mesial temporal lobe epilepsy after MR-guided laser interstitial thermal therapy: a single-institution experience.

OBJECTIVE: Piriform cortex (PC) is one of the critical structures in the epileptogenesis of mesial temporal lobe epilepsy (mTLE), but its role is poorly understood. The authors examined the utility of apparent diffusion coefficient (ADC; an MR-based marker of tissue pathology) of the PC as a predictor of seizure outcome in patients with mTLE undergoing MR-guided laser interstitial thermal therapy (MRgLITT). METHODS: A total of 33 patients diagnosed with mTLE who underwent MRgLITT at the authors' institution were included in the study. The 6-month postoperative seizure outcomes were classified using the International League Against Epilepsy (ILAE) system as good (complete seizure freedom, ILAE class I) and poor (seizure present, ILAE classes II-VI). The PC and ablation volumes were manually segmented from both the preoperative and intraoperative MRI sequences, respectively. The mean ADC intensities of 1) preablation PC; 2) total ablation volume; 3) ablated portion of PC; and 4) postablation residual PC were calculated and compared between good and poor outcome groups. Additionally, the preoperative PC volumes and proportion of PC volume ablated were examined and compared between the subjects in the two outcome groups. RESULTS: The mean age at surgery was 36.5 ± 3.0 years, and the mean follow-up duration was 1.9 ± 0.2 years. Thirteen patients (39.4%) had a good outcome. The proportion of PC ablated was significantly associated with seizure outcome (10.16 vs 3.30, p < 0.05). After accounting for the variability in diffusion tensor imaging acquisition parameters, patients with good outcome had a significantly higher mean ADC of the preablation PC (0.3770 vs -0.0108, p < 0.05) and the postoperative residual PC (0.4197 vs 0.0309, p < 0.05) regions compared to those with poor outcomes. No significant differences in ADC of the ablated portion of PC were observed (0.2758 vs -0.4628, p = 0.12) after performing multivariate analysis. CONCLUSIONS: A higher proportion of PC ablated was associated with complete seizure freedom. Preoperative and postoperative residual ADC measures of PC were significantly higher in the good seizure outcome group in patients with mTLE who underwent MRgLITT, suggesting that ADC analysis can assist with postablation outcome prediction and patient stratification.

Piriform Cortex Ablation Volume Is Associated With Seizure Outcome in Mesial Temporal Lobe Epilepsy.

BACKGROUND: Growing evidence suggests that piriform cortex resection during anterior temporal lobectomy is important for achieving good seizure outcome in mesial temporal lobe epilepsy (mTLE). However, the relationship between seizure outcome and piriform cortex ablation during MR-guided laser interstitial thermal therapy (MRgLITT) remains unclear. OBJECTIVE: To determine whether ablation of piriform cortex was associated with seizure outcome in patients with mTLE undergoing MRgLITT. METHODS: We performed preablation and postablation volumetric analyses of hippocampus, amygdala, piriform cortex, and ablation volumes in patients with mTLE who underwent MRgLITT at our institution from 2014 to 2019. RESULTS: Thirty nine patients with mTLE were analyzed. In univariate logistic regression, percent piriform cortex ablation was associated with International League Against Epilepsy (ILAE) class 1 at 6 months (odds ratio [OR] 1.051, 95% CI [1.001-1.117], P = .045), whereas ablation volume, percent amygdala ablation, and percent hippocampus ablation were not ( P > .05). At 1 year, ablation volume was associated with ILAE class 1 (OR 1.608, 95% CI [1.071-2.571], P = .021) while percent piriform cortex ablation became a trend (OR 1.050, 95% CI [0.994-1.109], P = .054), and both percent hippocampus ablation and percent amygdala ablation were not significantly associated with ILAE class 1 ( P > .05). In multivariable logistic regression, only percent piriform cortex ablation was a significant predictor of seizure freedom at 6 months (OR 1.085, 95% CI [1.012-1.193], P = .019) and at 1 year (OR 1.074, 95% CI [1.003-1.178], P = .041). CONCLUSION: Piriform cortex ablation volume is associated with seizure outcome in patients with mTLE undergoing MRgLITT. The piriform cortex should be considered a high yield ablation target to achieve good seizure outcome.

Advances in monitoring for acute spinal cord injury: a narrative review of current literature.

Spinal cord injury (SCI) is a devastating condition that affects about 17,000 individuals every year in the United States, with approximately 294,000 people living with the ramifications of the initial injury. After the initial primary injury, SCI has a secondary phase during which the spinal cord sustains further injury due to ischemia, excitotoxicity, immune-mediated damage, mitochondrial dysfunction, apoptosis, and oxidative stress. The multifaceted injury progression process requires a sophisticated injury-monitoring technique for an accurate assessment of SCI patients. In this narrative review, we discuss SCI monitoring modalities, including pressure probes and catheters, micro dialysis, electrophysiologic measures, biomarkers, and imaging studies. The optimal next-generation injury monitoring setup should include multiple modalities and should integrate the data to produce a final simplified assessment of the injury and determine markers of intervention to improve patient outcomes.

Association of intraoperative end-tidal carbon dioxide level with ablation volume during magnetic resonance-guided laser interstitial thermal therapy for mesial temporal lobe epilepsy.

OBJECTIVE: Maximal safe ablation of target structures during magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) is critical to achieving good seizure outcome in patients with mesial temporal lobe epilepsy (mTLE). The authors sought to determine whether intraoperative physiological variables are associated with ablation volume during MRgLiTT. METHODS: Patients with mTLE who underwent MRgLiTT at our institution from 2014 to 2019 were retrospectively analyzed. Ablation volume was determined with volumetric analysis of intraoperative postablation MR images. Physiological parameters (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP], end-tidal carbon dioxide [ETCO2]) measured 40 minutes prior to ablation were analyzed. Univariate and multivariate regression analyses were performed to determine independent predictors of ablation volume. RESULTS: Forty-four patients met the inclusion criteria. The median (interquartile range) ablation volume was 4.27 (2.92-5.89) cm3, and median ablation energy was 7216 (6402-8784) J. The median MAP, SBP, DBP, and ETCO2 values measured during the 40-minute period leading up to ablation were 72.8 (66.2-81.5) mm Hg, 104.4 (96.4-114.4) mm Hg, 62.4 (54.1-69.8) mm Hg, and 34.1 (32.0-36.2) mm Hg, respectively. In univariate analysis, only total laser energy (r = 0.464, p = 0.003) and 40-minute average ETCO2 (r = -0.388, p = 0.012) were significantly associated with ablation volume. In multivariate analysis, only ETCO2 ≤ 33 mm Hg (p = 0.001) was significantly associated with ablation volume. CONCLUSIONS: Total ablation energy and ETCO2, but not blood pressure, may significantly affect ablation volume in mTLE patients undergoing MRgLiTT. Mild hypocapnia was associated with increased extent of ablation. Intraoperative monitoring and modulation of ETCO2 may help improve extent of ablation, prediction of ablation volume, and potentially seizure outcome.

Spine Image Guidance and Robotics: Exposure, Education, Training, and the Learning Curve.

The use of intraoperative robotics and imaging for spine surgery has been shown to be safe, efficacious, and beneficial to patients, offering accurate placement of instrumentation, decreased operative time and blood loss, and improved postoperative outcomes. Despite these proven benefits, it has yet to be uniformly adopted. One of the major barriers for universal adoption of intraoperative robotics is the learning curve for this complex technology, in conjunction with a lack of formalized training. These same obstacles for universal adoption were faced in the introduction of surgical technology in other disciplines, and the use of this technology has become the standard of care in some of those specialties. Part of the success and widespread implementation of prior novel technology was the introduction of formalized training systems, which are currently lacking in advanced spine surgical technology. Therefore, the future success of intraoperative robotics and imaging for spine surgery depends on the creation of a formalized training system. We detail the best techniques for surgical pedagogy, as well as propose a comprehensive curriculum.

Apparent diffusion coefficient is associated with seizure outcome after magnetic resonance-guided laser interstitial thermal therapy for mesial temporal lobe epilepsy.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) is becoming a first-line surgical therapy for mesial temporal lobe epilepsy (mTLE) due to good seizure control and low complication risk. However, seizure outcomes after MRgLiTT remain highly variable and there is a need to improve patient selection and post-operative prognostication. In this retrospective study, we investigated whether the pre-operative MRI-derived apparent diffusion coefficient (ADC), used as a marker of tissue pathology in the mesial temporal structures could help predict seizure outcome. METHODS: Thirty-five patients who underwent MRgLiTT at our institution between 2014 and 2019 were included in the study. Demographic and clinical data were retrospectively collected. Seizure outcome was defined as good (ILAE Class I-II) and poor (ILAE Class III-VI). Volumetrics were performed on pre-ablation hippocampus and amygdala. Ablation volumes, and the proportion of ablated hippocampus and amygdala calculated via their respective mean voxel-wise ADC intensities were quantified from pre-operative and intra-operative post-ablation MRIs and statistically compared between the two outcome cohorts. Univarate and multivariate regression analysis was performed to identify demographic, clinical, and radiographic predictors of seizure outcome. RESULTS: Mean age at LiTT was 36 years and 14 (40 %) were female. Mean follow-up duration was 1.90 ± 0.17 years. Twenty-seven (77 %) patients had mesial temporal sclerosis. There was no significant difference in the ablation volumes and proportion of ablated volume of hippocampus and amygdala between the two outcome groups. Patients with good seizure outcome had significantly higher normalized ADC intensities in the ablated mesial temporal structures compared to those with poor outcome (0.01 ± 0.08 vs.-0.29 ± 0.06; p = 0.015). CONCLUSIONS: mTLE patients with higher ADC intensities in the ablated regions of the hippocampus and the amygdala are more likely to have good seizure outcome following MRgLiTT. Our results suggest that pre-operative ADC analysis may improve both patient selection and epileptogenic zone targeting during MRgLiTT. Further investigation with large, prospective cohorts is needed to validate the clinical utility of ADC in improving seizure outcome following MRgLiTT.

Development of a Smart Hospital Assistant: Integrating Artificial Intelligence and a Voice-User Interface for Improved Surgical Outcomes.

Patient safety and efficiency are top priorities in any surgical procedure. One effective way to achieve these objectives is to automate the logistical and routine tasks that occur in the operating suite. Inspired by smart assistant technology already widely used in the consumer sector, we engineered the Smart Hospital Assistant (SHA), a smart, voice-controlled virtual assistant that handles natural speech recognition while executing non-surgical functions to aid any surgery. In simulated procedures, the SHA reduced operating time, optimized surgical staff resources, and reduced the number of major touch-points that can lead to surgical site infections. The SHA holds promise not only for use in the operating theater, but also in understaffed healthcare environments where automation can improve healthcare delivery.

Perspective: Phase Amplitude Coupling-Based Phase-Dependent Neuromodulation in Parkinson's Disease.

Deep brain stimulation (DBS) is an effective surgical therapy for Parkinson's disease (PD). However, limitations of the DBS systems have led to great interest in adaptive neuromodulation systems that can dynamically adjust stimulation parameters to meet concurrent therapeutic demand. Constant high-frequency motor cortex stimulation has not been remarkably efficacious, which has led to greater focus on modulation of subcortical targets. Understanding of the importance of timing in both cortical and subcortical stimulation has generated an interest in developing more refined, parsimonious stimulation techniques based on critical oscillatory activities of the brain. Concurrently, much effort has been put into identifying biomarkers of both parkinsonian and physiological patterns of neuronal activities to drive next generation of adaptive brain stimulation systems. One such biomarker is beta-gamma phase amplitude coupling (PAC) that is detected in the motor cortex. PAC is strongly correlated with parkinsonian specific motor signs and symptoms and respond to therapies in a dose-dependent manner. PAC may represent the overall state of the parkinsonian motor network and have less instantaneously dynamic fluctuation during movement. These findings raise the possibility of novel neuromodulation paradigms that are potentially less invasiveness than DBS. Successful application of PAC in neuromodulation may necessitate phase-dependent stimulation technique, which aims to deliver precisely timed stimulation pulses to a specific phase to predictably modulate to selectively modulate pathological network activities and behavior in real time. Overcoming current technical challenges can lead to deeper understanding of the parkinsonian pathophysiology and development of novel neuromodulatory therapies with potentially less side-effects and higher therapeutic efficacy.

Disparities in Long-Acting Reversible Contraceptive Utilization among Married Women in Ethiopia: Findings of the Ethiopian Demographic and Health Survey.

BACKGROUND: Long-acting contraceptive methods, subdermal implants, and intrauterine devices are reliable, safe, and cost-effective family planning methods. However, these methods are not widely used in Ethiopia despite government effort to increase access. The study is aimed at assessing the rate of utilization of long-acting contraceptive methods among married women and associated factors. METHOD: We analyzed the 2016 Ethiopian Demographic and Health Survey dataset. A total of 2045 married women of reproductive age group, who were using any modern contraceptive method at the time of the survey, were included in the study. Descriptive statistics were computed to characterize the study participants. Bivariate and multivariable logistic regression analyses were performed to identify associated factors, reporting odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULT: The multivariable analyses showed that women educational status, parity, religion, previous history of abortion, desire for more child, and region where the respondents reside were significantly the factors that determine the utilization of long-acting contraceptive. There is a significant regional disparity in long-acting contraceptive utilization. Compared to women residing in Tigray region, those who live in other regions (Afar-Somali, Oromia, Amhara, Benishangul Gumz-Gambela, and Southern Nations Nationalities and People) have low likelihood of using long-acting contraceptive methods. CONCLUSION: Utilization of long-acting family planning method is low in Ethiopia. There is a significant regional disparity in utilizing these methods. Policy makers should promote culture-sensitive and tailored interventions to improve the utilization of long-acting family planning methods.

Between-tumor and within-tumor heterogeneity in invasive potential.

For women with access to healthcare and early detection, breast cancer deaths are caused primarily by metastasis rather than growth of the primary tumor. Metastasis has been difficult to study because it happens deep in the body, occurs over years, and involves a small fraction of cells from the primary tumor. Furthermore, within-tumor heterogeneity relevant to metastasis can also lead to therapy failures and is obscured by studies of bulk tissue. Here we exploit heterogeneity to identify molecular mechanisms of metastasis. We use "organoids", groups of hundreds of tumor cells taken from a patient and grown in the lab, to probe tumor heterogeneity, with potentially thousands of organoids generated from a single tumor. We show that organoids have the character of biological replicates: within-tumor and between-tumor variation are of similar magnitude. We develop new methods based on population genetics and variance components models to build between-tumor and within-tumor statistical tests, using organoids analogously to large sibships and vastly amplifying the test power. We show great efficiency for tests based on the organoids with the most extreme phenotypes and potential cost savings from pooled tests of the extreme tails, with organoids generated from hundreds of tumors having power predicted to be similar to bulk tests of hundreds of thousands of tumors. We apply these methods to an association test for molecular correlates of invasion, using a novel quantitative invasion phenotype calculated as the spectral power of the organoid boundary. These new approaches combine to show a strong association between invasion and protein expression of Keratin 14, a known biomarker for poor prognosis, with p = 2 × 10-45 for within-tumor tests of individual organoids and p < 10-6 for pooled tests of extreme tails. Future studies using these methods could lead to discoveries of new classes of cancer targets and development of corresponding therapeutics. All data and methods are available under an open source license at https://github.com/baderzone/invasion_2019.

Detection of prostate cancer in multiparametric MRI using random forest with instance weighting.

A prostate computer-aided diagnosis (CAD) based on random forest to detect prostate cancer using a combination of spatial, intensity, and texture features extracted from three sequences, T2W, ADC, and B2000 images, is proposed. The random forest training considers instance-level weighting for equal treatment of small and large cancerous lesions as well as small and large prostate backgrounds. Two other approaches, based on an AutoContext pipeline intended to make better use of sequence-specific patterns, were considered. One pipeline uses random forest on individual sequences while the other uses an image filter described to produce probability map-like images. These were compared to a previously published CAD approach based on support vector machine (SVM) evaluated on the same data. The random forest, features, sampling strategy, and instance-level weighting improve prostate cancer detection performance [area under the curve (AUC) 0.93] in comparison to SVM (AUC 0.86) on the same test data. Using a simple image filtering technique as a first-stage detector to highlight likely regions of prostate cancer helps with learning stability over using a learning-based approach owing to visibility and ambiguity of annotations in each sequence.