Calibration-free structured-light-based 3D scanning system in laparoscope for robotic surgery.

Accurate 3D shape measurement is crucial for surgical support and alignment in robotic surgery systems. Stereo cameras in laparoscopes offer a potential solution; however, their accuracy in stereo image matching diminishes when the target image has few textures. Although stereo matching with deep learning has gained significant attention, supervised learning requires a large dataset of images with depth annotations, which are scarce for laparoscopes. Thus, there is a strong demand to explore alternative methods for depth reconstruction or annotation for laparoscopes. Active stereo techniques are a promising approach for achieving 3D reconstruction without textures. In this study, a 3D shape reconstruction method is proposed using an ultra-small patterned projector attached to a laparoscopic arm to address these issues. The pattern projector emits a structured light with a grid-like pattern that features node-wise modulation for positional encoding. To scan the target object, multiple images are taken while the projector is in motion, and the relative poses of the projector and a camera are auto-calibrated using a differential rendering technique. In the experiment, the proposed method is evaluated by performing 3D reconstruction using images obtained from a surgical robot and comparing the results with a ground-truth shape obtained from X-ray CT.

Single and multi-frame auto-calibration for 3D endoscopy with differential rendering.

The use of 3D measurement in endoscopic images offers practicality in cancer diagnosis, computer-assisted interventions, and making annotations for machine learning training data. An effective approach is the implementation of an active stereo system, using a micro-sized pattern projector and an endoscope camera, which has been intensively developed. One open problem for such a system is the necessity of strict and complex calibration of the projector-camera system to precisely recover the shapes. Moreover, since the head of an endoscope should have enough elasticity to avoid harming target objects, the positions of the pattern projector cannot be tightly fixed to the head, resulting in limited accuracy. A straightforward approach to the problem is applying auto-calibration. However, it requires special markers in the pattern or a highly accurate initial position for stable calibration, which is impractical for real operation. In the paper, we propose a novel auto-calibration method based on differential rendering techniques, which are recently proposed and drawing wide attention. To apply the method to an endoscopic system, where a diffractive optical element (DOE) is used, we propose a technique to simultaneously estimate the focal length of the DOE as well as the extrinsic parameters between a projector and a camera. We also propose a multi-frame optimization algorithm to jointly optimize the intrinsic and extrinsic parameters, relative pose between frames, and the entire shape.Clinical relevance- One-shot endoscopic measurement of depth information is a practical solution for cancer diagnosis, computer-assisted interventions, and making annotations for machine learning training data.

A New Technical Approach for Cross-species Examination of Neuronal Wiring and Adult Neuron-glia Functions.

Advances in single cell sequencing have enabled the identification of a large number of genes, expressed in many different cell types, and across a variety of model organisms. In particular, the nervous system harbors an immense number of interacting cell types, which are poorly characterized. Future loss- and gain-of-function experiments will be essential in determining how novel genes play critical roles in diverse cellular, as well as evolutionarily adapted, contexts. However, functional analysis across species is often hampered by technical limitations, in non-genetic animal systems. Here, we describe a new single plasmid system, misPiggy. The system is based around the hyperactive piggyBac transposon system, which combines stable genomic integration of transgenes (for long-term expression) with large cargo capacity. Taking full advantage of these characteristics, we engineered novel expression modules into misPiggy that allow for cell-type specific loss- and gain-of-gene function. These modules work widely across species from frog to ferret. As a proof of principle, we present a loss-of-function analysis of the neuronal receptor Deleted in Colorectal Cancer (DCC) in retinal ganglion cells (RGCs) of Xenopus tropicalis tadpoles. Single axon tracings of mosaic knock-out cells reveal a specific cell-intrinsic requirement of DCC, specifically in axonal arborization within the frog tectum, rather than retina-to-brain axon guidance. Furthermore, we report additional technical advances that enable temporal control of knock-down or gain-of-function analysis. We applied this to visualize and manipulate labeled neurons, astrocytes and other glial cells in the central nervous system (CNS) of mouse, rat and ferret. We propose that misPiggy will be a valuable tool for rapid, flexible and cost-effective screening of gene function across a variety of animal models.

A pathological complete response after nivolumab plus ipilimumab therapy for DNA mismatch repair-deficient/microsatellite instability-high metastatic colon cancer: A case report.

The standard treatment for colorectal cancer has always been surgery and chemotherapy, which may be used in combination to treat patients. Immune checkpoint inhibitors have been a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair. However, little information is available about their use in neoadjuvant and conversion settings with only a few case reports and only one phase 2 trial. The present study reports the case of a large, locally advanced right-sided metastatic deficient mismatch repair/microsatellite instability-high colon cancer, which showed a pathological complete response after combination treatment with nivolumab and ipilimumab. To the best of our knowledge, resected metastatic colon cancer with a pathological complete response after treatment using dual immune checkpoint inhibitors has not been previously reported. Overall, this case report suggests the use of immune checkpoint inhibitors before colorectal surgery.

Outcomes of lung metastasis from pancreatic cancer: A nationwide multicenter analysis.

BACKGROUND: Although distant metastasis from pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, some single center studies reported that lung metastasis has a favorable prognosis. The aim of this study is to evaluate the prognostic value of site-specific metastasis after pancreatectomy for PDAC, with a focus on lung metastasis. METHODS: Data from 117 cases of lung metastasis after pancreatectomy were collected retrospectively from 23 institutions in Japan. To compare the sites of metastasis we also collected the data of 134 patients with liver only metastasis, 67 patients with peritoneal only metastasis and 121 patients with locoregional recurrence alone. RESULTS: In patients with lung only metastasis, the median time from recurrence to death (RTD) was 23.1 months, which was better in comparison to other sites of recurrence. In lung metastasis group, the patients who underwent pulmonary resection had better long-term outcomes in comparison to those who did not. (RTD: 29.2 vs 15.2, P < .001). In the multivariate analysis, solitary metastasis (HR 5.03; 95% CI 1.195-21.144, P = .022) and postoperative chemotherapy (HR 14.089; 95% CI 1.729-114.77, P = .023) were identified as significant prognostic factors after lung resection. CONCLUSIONS: Surgical resection is a favorable option for selected patients with a solitary lung metastasis and for whom adjuvant chemotherapy can be administrated.

A locally advanced pancreatic body cancer presenting common bile duct invasion resected via distal pancreatectomy after gemcitabine plus nab-paclitaxel chemotherapy: A case report.

INTRODUCTION: The locally advanced pancreatic cancer has been steadily recognized as a potentially curable disease by a combination of chemotherapy and surgery. The remarkable effect of advanced chemotherapy would help surgeons do a function-preserving operation for advanced pancreatic cancer. PRESENTATION OF CASE: A 73-year-old woman presenting with obstructive jaundice was diagnosed to have a 3-cm pancreatic body cancer invading the celiac axis (CA), superior mesenteric artery (SMA), portal/splenic vein confluence, and the common bile duct (CBD). A plastic internal stent tube was placed endoscopically. After 11 cycles (231 days) of a weekly doublet chemotherapy with 1000 mg/m2 of gemcitabine and 125 mg/m2 of albumin-bound paclitaxel, the tumor shrunk based on imaging done every four months during chemotherapy, with residual periarterial high-density area around CA and proximal SMA and the patient was referred for surgery. During the operation, the absence of cancer cells was confirmed at (1) the origin of the proper hepatic artery, gastroduodenal artery and the left gastric artery, and (2) pancreatic cut stump along the right border of the portal vein; thus, distal pancreatectomy with coeliac axis resection was done. The patient had postoperative adjuvant chemotherapy with 100 mg/day of tegafur/gimeracil/oteracil for half a year and is currently alive and well, without signs of recurrence and diabetes mellitus a year after surgery. DISCUSSION: Although surgical techniques aimed at local radicality are important, especially for conversion surgery for locally advanced pancreatic cancer, surgeons should consider the balance between radicality, safety, and functional preservation of surgery.

An anatomical review of various superior mesenteric artery-first approaches during pancreatoduodenectomy for pancreatic cancer.

When pancreatic head cancer invades the superior mesenteric artery (SMA), attempts at curative resection are aborted. Preoperative imaging diagnostics to determine the surgical curability have yet to surpass the intraoperative information acquired via inspection, palpation, and trial dissection. Pancreatoduodenectomy (PD) is a standard measure for treating periampullary cancers. In conventional PD, SMA invasion is usually identified by dissecting the retroportal lamina, which connects the uncinate process and SMA nerve plexus after dividing the neck of the pancreas. During PD for pancreatic head cancer, this retroperitoneal margin frequently vitiates surgical curability. SMA-first approaches during PD are methods where the SMA is dissected first by severing the posterior pancreatic capsule to assess the SMA involvement of pancreatic cancer early in the operation. The first report of such an approach prompted subsequent reports of various maneuvers that are now known collectively as "artery-first" approaches. We herein review those approaches by classifying them according to (1) the side of the mesocolon from where the SMA approach occurs (supracolic or infracolic) and (2) the direction of access (right or left and anterior or posterior). The steps of the reported PD procedures are numbered according to a timeline and summarized using anatomical division of the SMA.

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab: A study protocol.

BACKGROUND: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. METHODS: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment." DISCUSSION: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

Visualization of the Retina in Intact Eyes of Mice and Ferrets Using a Tissue Clearing Method.

Purpose: Visualization of specific cells and structures in intact organs would greatly facilitate our knowledge about pathological changes; therefore, a tissue clearing method applicable to the intact eye may be valuable. Here we report a novel imaging method for the retina using the hyperhydration-based tissue clearing technique CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational Analysis). Methods: Eyes of Institute of Cancer Research (ICR) mice, C57BL/6 mice, and normally pigmented sable ferrets (Mustela putorius furo) were used. Intact eyes were subjected to CUBIC, melanin bleaching with H2O2, and immunostaining. Images of the retina in intact eyes were taken using epifluorescence microscopes and confocal microscopes. Results: The combination of melanin bleaching and CUBIC efficiently made the eyes of C57BL/6 mice transparent. By combining melanin bleaching, CUBIC, and immunostaining, we succeeded in visualization of retinal structures from the outside of the intact eyes of mice. Furthermore, we found that our methods were applicable not only to mouse eyes but also to ferret eyes, which are much larger than those of mice. Conclusions: Our method was useful for visualizing specific cells and structures in the retina of intact eyes with single-cell resolution without making tissue sections. Translational Relevance: This simple and efficient method can be applicable to various rodent models, including those associated with glaucoma or myopia, and will facilitate evaluating the effects of novel therapy for relevant eye diseases by visualizing changes from the retina to the sclera at both molecular and macroscopic levels simultaneously in a whole-eye preparation.

Mass-forming hepatic cryptococcosis: a mimicker of metastatic tumors.

This report provides the first imaging report of isolated intrahepatic cryptococcosis. An 83-year-old man was incidentally pointed out of hepatic nodules. CT revealed four well-defined nodules of 21 mm, 15 mm, 7 mm, and 5 mm in diameter without contrast enhancement. Two nodules displayed central hyperattenuation and the others were totally hyperattenuating. MRI showed that the nodules were hypointense relative to normal liver parenchyma on T1- and T2-weighted images. 18F-FDG PET imaging revealed no obvious increased uptake of nuclear species into the liver nodules. Partial resection of the three largest hepatic nodules was performed based on a preoperative diagnosis of hepatic metastasis from known sigmoid colon cancer. All three resected nodules were composed mainly of necrotic tissue with peripheral histiocytic aggregates and numerous yeast-like cells. The final diagnosis was hepatic cryptococcosis.

Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice.

Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp-/-), filaggrin (Flgft/ft and Flg-/-), filaggrin-hornerin (FlgHrnr-/-), and bleomycin hydrolase (Blmh-/-) were investigated. Sasp-/- and Flg-/- were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp-/-. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.

Simultaneous shape and camera-projector parameter estimation for 3D endoscopic system using CNN-based grid-oneshot scan.

For effective in situ endoscopic diagnosis and treatment, measurement of polyp sizes is important. For this purpose, 3D endoscopic systems have been researched. Among such systems, an active stereo technique, which projects a special pattern wherein each feature is coded, is a promising approach because of simplicity and high precision. However, previous works of this approach have problems. First, the quality of 3D reconstruction depended on the stabilities of feature extraction from the images captured by the endoscope camera. Second, due to the limited pattern projection area, the reconstructed region was relatively small. In this Letter, the authors propose a learning-based technique using convolutional neural networks to solve the first problem and an extended bundle adjustment technique, which integrates multiple shapes into a consistent single shape, to address the second. The effectiveness of the proposed techniques compared to previous techniques was evaluated experimentally.

A structured light laser probe for gastrointestinal polyp size measurement: a preliminary comparative study.

BACKGROUND AND STUDY AIMS: Polyp size measurement is an important diagnostic step during gastrointestinal endoscopy, and is mainly performed by visual inspection. However, lack of depth perception and objective reference points are acknowledged factors contributing to measurement errors in polyp size. In this paper, we describe the proof-of-concept of a polyp measurement device based on structured light technology for future endoscopes. PATIENTS AND METHODS: Measurement accuracy, time, user confidence, and satisfaction were evaluated for polyp size assessment by (a) visual inspection, (b) open biopsy forceps of known size, (c) ruled snare, and (d) structured light probe, for a total of 392 independent polyp measurements in ex vivo porcine stomachs. RESULTS: Visual assessment resulted in a median estimation error of 2.2 mm, IQR = 2.6 mm. The proposed probe can reduce the error to 1.5 mm, IQR = 1.67 mm ( P  = 0.002, 95 %CI) and its performance was found to be statistically similar to using forceps for reference ( P  = 0.81, 95 %CI) or ruled snare ( P  = 0.99, 95 %CI), while not occluding the tool channel. Timing performance with the probe was measured to be on average 54.75 seconds per polyp. This was significantly slower than visual assessment (20.7 seconds per polyp, P  = 0.005, 95 %CI) but not significantly different from using a snare (68.5 seconds per polyp, P  = 0.73, 95 %CI). However, the probe's timing performance was partly due to lens cleaning problems in our preliminary design. Reported average satisfaction on a 0 - 10 range was highest for the proposed probe (7.92), visual assessment (7.01), and reference forceps (7.82), while significantly lower for snare users with a score of 4.42 ( P  = 0.035, 95 %CI). CONCLUSIONS: The common practice of visual assessment of polyp size was found to be significantly less accurate than tool-based assessment, but easy to carry out. The proposed technology offers an accuracy on par with using a reference tool or ruled snare with the same satisfaction levels of visual assessment and without occluding the tool channel. Further study will improve the design to reduce the operating time by integrating the probe within the scope tip.

Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals.

Leptomeningeal glioneuronal heterotopia (LGH) is a focal malformation of the cerebral cortex and frequently found in patients with thanatophoric dysplasia (TD). The pathophysiological mechanisms underlying LGH formation are still largely unclear because of difficulties in obtaining brain samples from human TD patients. Recently, we established a new animal model for analysing cortical malformations of human TD by utilizing our genetic manipulation technique for gyrencephalic carnivore ferrets. Here we investigated the pathophysiological mechanisms underlying the formation of LGH using our TD ferrets. We found that LGH was formed during corticogenesis in TD ferrets. Interestingly, we rarely found Ki-67-positive and phospho-histone H3-positive cells in LGH, suggesting that LGH formation does not involve cell proliferation. We uncovered that vimentin-positive radial glial fibers and doublecortin-positive migrating neurons were accumulated in LGH. This result may indicate that preferential cell migration into LGH underlies LGH formation. Our findings provide novel mechanistic insights into the pathogenesis of LGH in TD.

Inflammation-free, gas-permeable, lightweight, stretchable on-skin electronics with nanomeshes.

Thin-film electronic devices can be integrated with skin for health monitoring and/or for interfacing with machines. Minimal invasiveness is highly desirable when applying wearable electronics directly onto human skin. However, manufacturing such on-skin electronics on planar substrates results in limited gas permeability. Therefore, it is necessary to systematically investigate their long-term physiological and psychological effects. As a demonstration of substrate-free electronics, here we show the successful fabrication of inflammation-free, highly gas-permeable, ultrathin, lightweight and stretchable sensors that can be directly laminated onto human skin for long periods of time, realized with a conductive nanomesh structure. A one-week skin patch test revealed that the risk of inflammation caused by on-skin sensors can be significantly suppressed by using the nanomesh sensors. Furthermore, a wireless system that can detect touch, temperature and pressure is successfully demonstrated using a nanomesh with excellent mechanical durability. In addition, electromyogram recordings were successfully taken with minimal discomfort to the user.

A case of an anomalous biliary tract diagnosed preoperatively.

We describe a 48-year-old man with cholecystolithiasis whose preoperative magnetic resonance cholangiopancreatography (MRCP) scan showed that the right accessory hepatic duct branching from the cystic duct dominated an anterior segment of the right hepatic lobe. We observed the right accessory hepatic duct using intraoperative cholangiography, and we were able to perform laparoscopic cholecystectomy without injuring it. He had no complication after discharge, and a drip-infusion cholangiography-computed tomography (DIC-CT) scan demonstrated that the right accessory hepatic duct was intact, and it dominated an anterior segment of the right hepatic lobe. During laparoscopic cholecystectomy, a bile duct injury is the most challenging perioperative complication. We selected MRCP preoperatively; however, if it is necessary for us to observe an anomalous biliary tract more precisely, we recommend selecting DIC-CT endoscopic retrograde cholangiopancreatography. Additionally, we think a bile duct injury can be avoided with intraoperative cholangiography, even if there is an anomalous biliary tract.

A case of multiple inflammatory hepatic pseudotumor protruding from the liver surface after colonic cancer.

INTRODUCTION: Inflammatory hepatic pseudotumor (IHPT) is an important benign liver disease because it is difficult to clinically and radiologically distinguish from malignant tumors. PRESENTATION OF CASE: Here, we describe a case of a 67-year-old male patient diagnosed with multiple inflammatory hepatic pseudotumors. The patient had undergone left hemicolectomy for descending colonic cancer (T3 N0 M0 stage IIA) 2 years prior. He underwent segment 6 and segment 7 partial hepatectomy because of suspected liver metastasis. The patient had an unremarkable postoperative course and was discharged 7days after surgery. Marked infiltration of inflammatory cells was observed on histological examination. The patient was finally diagnosed with IHPT of the fibrohistiocytic type. DISCUSSION: Repeated imaging studies over 1 month showed the spontaneous regression of the hepatic tumors. Therefore, knowledge regarding this condition is necessary to allow for treatment, even in the absence of experience. During examination, it may be important to ascertain lesion size. Moreover, percutaneous needle biopsy and follow-up examinations are necessary for cases of suspected IHPT. CONCLUSION: Hepatectomy should be considered if the lesion is suspected to be an IHPT.

Clinical outcomes of self-expandable metal stent (SEMS) placement as palliative treatment for malignant colorectal obstruction: A single-center study from Japan.

OBJECTIVES: We aimed to assess the efficacy of self-expanding metal stent (SEMS) implantation as palliative treatment for malignant colorectal obstruction. METHODS: We retrospectively reviewed the records of patients with malignant colorectal obstruction who underwent SEMS insertion as palliative treatment in our hospital between March 2013 and December 2016. We analyzed demographic, clinical, and operative characteristics. RESULTS: A total of 13 patients (8 males, 5 females; median age, 80.1 years) were reviewed. Tumor location included the left colon, rectum, and right colon in 38.5%, 38.5%, and 23% of the patients, respectively. Advanced and early colorectal cancer were noted in 7 (63.6%) and 4 (36.4%) cases, respectively. The mean ColoRectal Obstruction Scoring System score was 0.92 before stenting and 3.92 after stenting. Oral intake was resumed at a median of 2.1 days after SEMS placement. Median stent patency was 7.6 months, and 69.2% of patients maintained stent patency until death or the end of follow-up. Stent-related adverse effects included: re-occlusion (4 cases, 30.8%); stent migration (1 case, 7.7%), and pain with tenesmus (2 cases, 15.4%). In patients with re-occlusion (median follow-up interval, 1.3 months), stent patency was maintained for a median of 10.3 months (early failure, within 3 months; late failure, >11 months). CONCLUSION: SEMS placement as a palliative treatment is likely to fail within a year, leading to re-occlusion. It is very important to maintain vigilant monitoring using X-ray, CT, and colonoscopy after SEMS placement, with close cooperation between the endoscopist and surgeon. A logistic framework involving careful follow-up, even in the absence of symptoms, and a combined team involving endoscopists and surgeons should be established to support re-intervention and surgery. We recommend vigilant monitoring of patients who received SEMS placement for palliation of malignant colorectal obstruction.

Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.

Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD.