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Purpose: To verify whether deep learning can be used to differentiate between carcinosarcomas (CSs) and endometrial carcinomas (ECs) using several magnetic resonance imaging (MRI) sequences. Material and methods: This retrospective study included 52 patients with CS and 279 patients with EC. A deep-learning model that uses convolutional neural networks (CNN) was trained with 572 T2-weighted images (T2WI) from 42 patients, 488 apparent diffusion coefficient of water maps from 33 patients, and 539 fat-saturated contrast-enhanced T1-weighted images from 40 patients with CS, as well as 1612 images from 223 patients with EC for each sequence. These were tested with 9-10 images of 9-10 patients with CS and 56 images of 56 patients with EC for each sequence, respectively. Three experienced radiologists independently interpreted these test images. The sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) for each sequence were compared between the CNN models and the radiologists. Results: The CNN model of each sequence had sensitivity 0.89-0.93, specificity 0.44-0.70, accuracy 0.83-0.89, and AUC 0.80-0.94. It also showed an equivalent or better diagnostic performance than the 3 readers (sensitivity 0.43-0.91, specificity 0.30-0.78, accuracy 0.45-0.88, and AUC 0.49-0.92). The CNN model displayed the highest diagnostic performance on T2WI (sensitivity 0.93, specificity 0.70, accuracy 0.89, and AUC 0.94). Conclusions: Deep learning provided diagnostic performance comparable to or better than experienced radiologists when distinguishing between CS and EC on MRI. [ABSTRACT FROM AUTHOR]

Odor signals are conveyed from the olfactory bulb (OB) to the olfactory cortex by two types of projection neurons, tufted cells and mitral cells, which differ in signal timing and firing frequency in response to odor inhalation. Whereas tufted cells respond with early-onset high-frequency burst discharges starting at the middle of the inhalation phase of sniff, mitral cells show odor responses with later-onset lower-frequency burst discharges. Since odor inhalation induces prominent gamma-oscillations of local field potentials (LFPs) in the OB during the transition period from inhalation to exhalation that accompany synchronized spike discharges of tufted cells and mitral cells, we addressed the question of whether the odor-induced gamma-oscillations encompass two distinct gamma-oscillatory sources, tufted cell and mitral cell subsystems, by simultaneously recording the sniff rhythms and LFPs in the OB of freely behaving rats. We observed that individual sniffs induced nested gamma-oscillations with two distinct parts during the inhalation-exhalation transition period: early-onset fast gamma-oscillations followed by later-onset slow gamma-oscillations. These results suggest that tufted cells carry odor signals with early-onset fast gamma-synchronization at the early phase of sniff, whereas mitral cells send them with later-onset slow gamma-synchronization. We also observed that each sniff typically induced both fast and slow gamma-oscillations during awake, whereas respiration during slowwave sleep and rapid-eye-movement sleep failed to induce these oscillations. These results suggest that behavioral states regulate the generation of sniff rhythm-paced fast and slow gamma-oscillations in the OB. [ABSTRACT FROM AUTHOR]

Granule cells in the olfactory bulb (OB) are continually produced and added into the neuronal circuit in the adult brain. Sensory input to the OB plays a key role in the survival of newly generated granule cells. Here, we examined in the adult mice whether there is a time window after the generation of new granule cells when their survival is strongly influenced by sensory input. New granule cells were labeled by BrdUrd injection, and the mice were deprived of sensory input unilaterally by naris cauterization. During the initial 14 days after BrdUrd labeling, the number of Brdurd-positive granule cells was similar for deprived and undeprived OBs. At 28 days or later, the BrdUrd-positive cell number remarkably decreased in the deprived OB. Cauterization at days 14-28 effectively reduced the number of BrdUrd-positive granule cells, whereas 2-week cauterization before or after this period produced little effect. Administration of diazepam, a GABAA receptor modulator, decreased the number of BrdUrd-positive granule cells. The diazepam administration was most effective at days 14-28. Histochemical examination showed that activation of caspase-3 was accompanied by apoptotic cell death of granule cells that was induced by sensory deprivation or diazepam administration. Double labeling with activated caspase-3 and BrdUrd indicated that granule cells at days 14-20 were most susceptible to cell death. These results indicate that there is a critical period when the survival of new granule cells is determined in a sensory experience-dependent manner and that the Pharmacological manipulation can mimic the effect of sensory deprivation. [ABSTRACT FROM AUTHOR]

During slowwave sleep, interareal communications via coordinated, slow oscillatory activities occur in the large-scale networks of the mammalian neocortex. Because olfactory cortex (OC) areas, which belong to paleocortex, show characteristic sharp-wave (SPW) activity during slow-wave sleep, we examined whether OC SPWs in freely behaving rats occur in temporal coordination with up- and downstates of the orbitofrontal cortex (OFC) slow oscillation. Simultaneous recordings of local field potentials and spike activities in the OC and OFC showed that during the downstate in the OFC, the OC also exhibited downstate with greatly reduced neuronal activity and suppression of SPW generation. OC SPWs occurred during two distinct phases of the upstate of the OFC: early-phase SPWs occurred at the start of upstate shortly after the down-to-up transition in the OFC, whereas late-phase SPWs were generated at the end of upstate shortly before the up-todown transition. Such temporal coordination between neocortical upand downstates and olfactory system SPWs was observed between the prefrontal cortex areas (OFC and medial prefrontal cortex) and the OC areas (anterior piriform cortex and posterior piriform cortex). These results suggest that during slow-wave sleep, OC and OFC areas communicate preferentially in specific time windows shortly after the down-to-up transition and shortly before the up-to-down transition. [ABSTRACT FROM AUTHOR]

During slow-wave sleep, anterior piriform cortex neurons show highly synchronized discharges that accompany olfactory cortex sharp waves (OC-SPWs). The OC-SPW-related synchronized activity of anterior piriform cortex neurons travel down to the olfactory bulb and is thought to be involved in the reorganization of bulbar neuronal circuitry. However, influences of the OC-SPW-related activity on other regions of the central olfactory system are still unknown. Olfactory tubercle is an area of OC and part of ventral striatum that plays a key role in reward-directed motivational behaviors. In this study, we show that in freely behaving rats, olfactory tubercle receives OC-SPW-associated synchronized inputs during slow-wave sleep. Local field potentials in the olfactory tubercle showed SPW-like activities that were in synchrony with OC-SPWs. Single-unit recordings showed that a subpopulation of olfactory tubercle neurons discharged in synchrony with OC-SPWs. Furthermore, correlation analysis of spike activity of anterior piriform cortex and olfactory tubercle neurons revealed that the discharges of anterior piriform cortex neurons tended to precede those of olfactory tubercle neurons. Current source density analysis in urethane-anesthetized rats indicated that the current sink of the OC-SPW-associated input was located in layer III of the olfactory tubercle. These results indicate that OC-SPW-associated synchronized discharges of piriform cortex neurons travel to the deep layer of the olfactory tubercle and drive discharges of olfactory tubercle neurons. The entrainment of olfactory tubercle neurons in the OC-SPWs suggests that OC-SPWs coordinate reorganization of neuronal circuitry across wide areas of the central olfactory system including olfactory tubercle during slow-wave sleep. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective analysis of magnetic resonance imaging (MRI) was conducted.Objective: This study aims to develop an automated system for the detection of spinal schwannoma, by employing deep learning based on object detection from MRI. The performance of the proposed system was verified to compare the performances of spine surgeons.Summary Of Background Data: Several MRI scans were conducted for the diagnoses of patients suspected to suffer from spinal diseases. Typically, spinal diseases do not involve tumors on the spinal cord, although a few tumors may exist at the unexpectable level or without symptom by chance. It is difficult to recognize these tumors; in some cases, these tumors may be overlooked. Hence, a deep learning approach based on object detection can minimize the probability of overlooking these tumors.Methods: Data from 50 patients with spinal schwannoma who had undergone MRI were retrospectively reviewed. Sagittal T1- and T2-weighted magnetic resonance imaging (T1WI and T2WI) were used in the object detection training and for validation. You Only Look Once version3 was used to develop the object detection system, and its accuracy was calculated. The performance of the proposed system was compared to that of two doctors.Results: The accuracies of the proposed object detection based on T1W1, T2W1, and both T1W1 and T2W1 were 80.3%, 91.0%, and 93.5%, respectively. The accuracies of the doctors were 90.2% and 89.3%.Conclusion: Automated object detection of spinal schwannoma was achieved. The proposed system yielded a high accuracy that was comparable to that of the doctors.Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Decisions concerning additional surgery after endoscopic resection of T1 colorectal cancer (CRC) are difficult because preoperative prediction of lymph node metastasis (LNM) is problematic. We investigated whether artificial intelligence can predict LNM presence, thus minimizing the need for additional surgery.Patients and Methods: Data on 690 consecutive patients with T1 CRCs that were surgically resected in 2001 - 2016 were retrospectively analyzed. We divided patients into two groups according to date: data from 590 patients were used for machine learning for the artificial intelligence model, and the remaining 100 patients were included for model validation. The artificial intelligence model analyzed 45 clinicopathological factors and then predicted positivity or negativity for LNM. Operative specimens were used as the gold standard for the presence of LNM. The artificial intelligence model was validated by calculating the sensitivity, specificity, and accuracy for predicting LNM, and comparing these data with those of the American, European, and Japanese guidelines.Results: Sensitivity was 100 % (95 % confidence interval [CI] 72 % to 100 %) in all models. Specificity of the artificial intelligence model and the American, European, and Japanese guidelines was 66 % (95 %CI 56 % to 76 %), 44 % (95 %CI 34 % to 55 %), 0 % (95 %CI 0 % to 3 %), and 0 % (95 %CI 0 % to 3 %), respectively; and accuracy was 69 % (95 %CI 59 % to 78 %), 49 % (95 %CI 39 % to 59 %), 9 % (95 %CI 4 % to 16 %), and 9 % (95 %CI 4 % - 16 %), respectively. The rates of unnecessary additional surgery attributable to misdiagnosing LNM-negative patients as having LNM were: 77 % (95 %CI 62 % to 89 %) for the artificial intelligence model, and 85 % (95 %CI 73 % to 93 %; P < 0.001), 91 % (95 %CI 84 % to 96 %; P < 0.001), and 91 % (95 %CI 84 % to 96 %; P < 0.001) for the American, European, and Japanese guidelines, respectively.Conclusions: Compared with current guidelines, artificial intelligence significantly reduced unnecessary additional surgery after endoscopic resection of T1 CRC without missing LNM positivity. [ABSTRACT FROM AUTHOR]

Background and study aims Invasive cancer carries the risk of metastasis, and therefore, the ability to distinguish between invasive cancerous lesions and less-aggressive lesions is important. We evaluated a computer-aided diagnosis system that uses ultra-high (approximately × 400) magnification endocytoscopy (EC-CAD). Patients and methods We generated an image database from a consecutive series of 5843 endocytoscopy images of 375 lesions. For construction of a diagnostic algorithm, 5543 endocytoscopy images from 238 lesions were randomly extracted from the database for machine learning. We applied the obtained algorithm to 200 endocytoscopy images and calculated test characteristics for the diagnosis of invasive cancer. We defined a high-confidence diagnosis as having a ≥ 90 % probability of being correct. Results Of the 200 test images, 188 (94.0 %) were assessable with the EC-CAD system. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were 89.4 %, 98.9 %, 94.1 %, 98.8 %, and 90.1 %, respectively. High-confidence diagnosis had a sensitivity, specificity, accuracy, PPV, and NPV of 98.1 %, 100 %, 99.3 %, 100 %, and 98.8 %, respectively. Conclusion: EC-CAD may be a useful tool in diagnosing invasive colorectal cancer. [ABSTRACT FROM AUTHOR]

Background and study aims: Optical diagnosis of colorectal polyps is expected to improve the cost-effectiveness of colonoscopy, but achieving a high accuracy is difficult for trainees. Computeraided diagnosis (CAD) is therefore receiving attention as an attractive tool. This study aimed to validate the efficacy of the latest CADmodel for endocytoscopy (380-fold ultra-magnifying endoscopy). Patients and methods: This international webbased trial was conducted between August and November 2015.A web-based test comprising one white-light and one endocytoscopic image of 205 small colorectal polyps (≤10mm) from 123 patients was undertaken by both CADand by endoscopists (three experts and ten non-experts from three countries). Outcome measures were accuracy in identifying neoplastic change in diminutive (≤5mm) and small (≤10mm) polyps, and accuracy in predicting post-polypectomy surveillance intervals according to current guidelines for high confidence optical diagnoses of diminutive polyps. Results: Of the 205 small polyps (147 neoplastic and 58 non-neoplastic), 139 were diminutive. CADwas accurate for 89% (95% confidence interval [CI] 83%-94%) of diminutive polyps and 89% (84%-93%) of small polyps, which was significantly greater than results for the non-experts (73% [71%-76%], P<0.001; and 76% [74%-78%], P<0.001, respectively) and comparable with the experts' results (90% [87%-93%], P=0.703; and 91% [89%-93%], P=0.106, respectively). The surveillance interval predicted by CADprovided 98% (93%-100%) and 96% (91%-99%) agreement with pathology-directed intervals of the European and American guidelines, respectively. Conclusions: The use of CADin endocytoscopy can be effective in the management of diminutive/ small colorectal polyps. [ABSTRACT FROM AUTHOR]

Anodor induces food-seeking behaviors when humans and animals learned to associate the odor with food, whereas the same odor elicits aversive behaviors following odor- danger association learning. It is poorly understood how central olfactory circuits transform the learned odor cue information into appropriate motivated behaviors. The olfactory tubercle (OT) is an intriguing area of the olfactory cortex in that it contains medium spiny neurons as principal neurons and constitutes a part of the ventral striatum. The OT is therefore a candidate area for participation in odor-induced motivated behaviors. Here we mapped c-Fos activation of medium spiny neurons in different domains of the mouse OT following exposure to learned odor cues. Mice were trained to associate odor cues to a sugar reward or foot shock punishment to induce odor-guided approach behaviors or aversive behaviors. Regardless of odorant types, the anteromedial domain of the OT was activated by learned odor cues that induced approach behaviors, whereas the lateral domain was activated by learned odor cues that induced aversive behaviors. In each domain, a largernumberof dopamine receptorD1type neurons were activated than D2 type neurons. These results indicate that specific domains of the OT represent odor-induced distinct motivated behaviors rather than odor stimuli, and raise the possibility that neuronal type-specific activation in individual domains of the OT plays crucial roles in mediating the appropriate learned odor-induced motivated behaviors. [ABSTRACT FROM AUTHOR]

Although it is well known that injury induces the generation of a substantial number of new olfactory sensory neurons (OSNs) in the adult olfactory epithelium (OE), it is not well understood whether olfactory sensory input influences the survival and maturation of these injury-induced OSNs in adults. Here, we investigated whether olfactory sensory deprivation affected the dynamic incorporation of newly generated OSNs 3, 7,14, and 28 d after injury in adult mice. Mice were unilaterally deprived of olfactory sensory input by inserting a silicone tube into their nostrils. Methimazole, an olfactotoxic drug, was also injected intraperitoneal to bilaterally ablate OSNs. The OE was restored to its preinjury condition with new OSNs by day 28. No significant differences in the numbers of olfactory marker proteinpositive mature OSNs or apoptotic OSNs were observed between the deprived and nondeprived sides 0 - 7 d after injury. However, between days 7 and 28, the sensory-deprived side showed markedly fewer OSNs and mature OSNs, but more apoptotic OSNs, than the nondeprived side. Intrinsic functional imaging of the dorsal surface of the olfactory bulb at day 28 revealed that responses to odor stimulation were weaker in the deprived side compared with those in the nondeprived side. Furthermore, prevention of cell death in new neurons 7-14 d after injury promoted the recovery of the OE. These results indicate that, in the adult OE, sensory deprivation disrupts compensatory OSN regeneration after injury and that newly generated OSNs have a critical time window for sensory-input-dependent survival 7-14 d after injury. [ABSTRACT FROM AUTHOR]

The olfactory bulb (OB) is one of the two major loci in the mammalian brain where newborn neurons are constantly integrated into the neural circuit during postnatal life. Newborn neurons are generated from neural stem cells in the subventricular zone (SVZ) of the lateral ventricle and migrate to the OB through the rostral migratory stream. The majority of these newborn neurons differentiate into inhibitory interneurons, such as granule cells and periglomerular cells. It has been reported that prolonged supply of newborn neurons leads to continuous addition/turnover of the interneuronal populations and contributes to functional integrity of the OB circuit. However, it is not still clear how and to what extent postnatal-born neurons contribute to OB neural circuit formation, and the functional role of postnatal neurogenesis in odor-related behaviors remains elusive. To address this question, here by using genetic strategies, we first determined the unique integration mode of newly born interneurons during postnatal development of the mouse OB. We then manipulated these interneuron populations and found that continuous postnatal neurogenesis in the SVZ-OB plays pivotal roles in flexible olfactory associative learning and memory. [ABSTRACT FROM AUTHOR]

The olfactory cortex is functionally isolated from the external odor world during slow-wave sleep. However, the neuronal activity pattern in the olfactory cortex and its functional roles during slow-wave sleep are not well understood. Here, we demonstrate in freely behaving rats that the anterior piriform cortex, a major area of the olfactory cortex, repeatedly generates sharp waves that are accompanied by synchronized discharges of numerous cortical neurons. Olfactory cortex sharp waves occurred relatively independently of hippocampal sharp waves. Current source density analysis showedthat sharp wave generation involvedthe participation of recurrent association fiber synapsesto pyramidal cells inthe olfactory cortex. During slow-wave sleep,the olfactory bulb showed sharp wavesthat were in synchrony with olfactory cortex sharp waves, indicatingthat olfactory cortex sharp waves drove synchronizedtop-down inputstothe olfactory bulb. Based onthese results, we speculatethatthe olfactory cortex sharp waves may play a role inthe reorganization of bulbar neuronal circuits during slow-wave sleep. [ABSTRACT FROM AUTHOR]

The glomerular layer of the mammalian olfactory bulb (OB) forms odorant receptor (OR) maps. Each OR map is structurally and functionally compartmentalized into zones (dorsal and ventral) and domains (DI and DII in the dorsal zone). We previously reported that glomeruli with similar molecular receptive range properties formed molecular feature clusters at stereotypical positions in the rat OB. However, the spatial arrangement of the molecular feature clusters with regard to the OR zones and domains has not been systematically examined. In this study, we optically mapped the molecular feature clusters of glomeruli within the domain and zone framework of the OB using domain-visible class II GFP transgenic mice. In all mice examined, fatty acid-responsive cluster A was located in the lateral part of domain DI, whereas clusters B, C, and D were arranged in an anterior to posterior order within domain DII. We also found a new cluster of glomeruli that respond to fox odor trimethyl-thiazoline and its structural analogs (heterocyclic odorants that contain sulfur and nitrogen atoms within the ring). This cluster (named cluster J) was located posterior to cluster D within the DII domain. These results show that molecular feature clusters correspond to specific subsets of glomeruli in selective domains of the OR map, suggesting that the molecular feature clusters represent specific ORs that have similar molecular receptive range properties and functional roles. [ABSTRACT FROM AUTHOR]

The projection of olfactory sensory neuron (OSN) axons from the olfactory epithelium (OE) to the olfactory bulb (OB) is highly organized but topographically complex. Evidence suggests that odorant receptor expression zones in the OE map to the OB about orthogonal axes. One candidate molecule for the formation of zone-specific targeting of OSN axon synapses onto the OB is the olfactory cell adhesion molecule (OCAM). OCAM+ OSNs are restricted to three of the four zones in the OE and project their axons to the ventral OB where they form synapses with mitral/tufted (M/T) cells. To determine when this zonal connection is established, we have examined OCAM expression in rat olfactory system, during seminal periods of glomerular formation. OCAM+ axons sort out in the ventral olfactory nerve layer of the OB before glomerular formation. Surprisingly, OCAM was also expressed transiently by subsets of M/T cell dendrites located in the dorsal OB. The expression of OCAM by OSN axons and M/T dendrites was asymmetrical; in the dorsal OB, OCAM- OSN axons synapsed on OCAM+ M/T dendrites, whereas in the ventral OB, OCAM+ OSN axons synapsed on OCAM- M/T dendrites. The restricted spatial map of OCAM+ M/T cells appeared earlier in development than the zonal segregation of OCAM+ OSN axons. Thus, OCAM on M/T cell dendrites may act in a spatiotemporal window to specify regions of the developing rat OB, thereby establishing a foundation for mapping of the OE zonal organization onto the OB. J. Comp. Neurol. 458:389–403, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]