Two-photon microscopic observation of cell-production dynamics in the developing mammalian neocortex in utero.

Morphogenesis and organ development should be understood based on a thorough description of cellular dynamics. Recent studies have explored the dynamic behaviors of mammalian neural progenitor cells (NPCs) using slice cultures in which three-dimensional systems conserve in vivo-like environments to a considerable degree. However, live observation of NPCs existing truly in vivo, as has long been performed for zebrafish NPCs, has yet to be established in mammals. Here, we performed intravital two-photon microscopic observation of NPCs in the developing cerebral cortex of H2B-EGFP or Fucci transgenic mice in utero. Fetuses in the uterine sac were immobilized using several devices and were observed through a window made in the uterine wall and the amniotic membrane while monitoring blood circulation. Clear visibility was obtained to the level of 300 µm from the scalp surface of the fetus, which enabled us to quantitatively assess NPC behaviors, such as division and interkinetic nuclear migration, within a neuroepithelial structure called the ventricular zone at embryonic day (E) 13 and E14. In fetuses undergoing healthy monitoring in utero for 60 min, the frequency of mitoses observed at the apical surface was similar to those observed in slice cultures and in freshly fixed in vivo specimens. Although the rate and duration of successful in utero observations are still limited (33% for ≥10 min and 14% for 60 min), further improvements based on this study will facilitate future understanding of how organogenetic cellular behaviors occur or are pathologically influenced by the systemic maternal condition and/or maternal-fetal relationships.

Effect of skin-transmitted vibration enhancement on vibrotactile perception.

Vibration on skin elicited by the mechanical interaction of touch between the skin and an object propagates to skin far from the point of contact. This paper investigates the effect of skin-transmitted vibration on vibrotactile perception. To enhance the transmission of high-frequency vibration on the skin, stiff tape was attached to the skin so that the tape covered the bottom surface of the index finger from the periphery of the distal interphalangeal joint to the metacarpophalangeal joint. Two psychophysical experiments with high-frequency vibrotactile stimuli of 250 Hz were conducted. In the psychophysical experiments, discrimination and detection thresholds were estimated and compared between conditions of the presence or the absence of the tape (normal bare finger). A method of limits was applied for the detection threshold estimation, and the discrimination task using a reference stimulus and six test stimuli with different amplitudes was applied for the discrimination threshold estimation. The stimulation was given to bare fingertips of participants. Result showed that the detection threshold was enhanced by attaching the tape, and the discrimination threshold enhancement by attaching the tape was confirmed for participants who have relatively large discrimination threshold under normal bare finger. Then, skin-transmitted vibration was measured with an accelerometer with the psychophysical experiments. Result showed that the skin-transmitted vibration when the tape was attached to the skin was larger than that when normal bare skin. There is a correlation between the increase in skin-transmitted vibration and the enhancement of the discrimination threshold.

Relation between gravitational and arm-movement direction in the mechanism of perception in bimanual steering.

This paper presents the effects of the opposing directions of gravity relative to right- and left-arm movement in bimanual steering. We developed a simulated steering system that permits independent left- and right-hand steering and torque presentations on a single axis, and independent measurements of the steering force exerted by each hand. In a steering force measurement experiment, left and right system units were mechanically combined to function as a single steering unit. Measurements of the force exerted by the participants with their left and right hands revealed that in human bimanual steering, the arm moving with gravity exerts a larger steering force than the one moving against gravity. In a steering force discrimination experiment, the system was mechanically configured to provide independence in both the function of the left and right steering units and the presentation of different left- and right-side steering torques. Each participant was then asked whether the steering force was felt to be larger on the left or the right during bimanual steering. The results of this experiment showed no difference between the left and the right arm in the discrimination threshold, but did reveal a perceptual bias in which the forces exerted in arm movements with gravity were perceived as being smaller than the forces exerted against gravity. Furthermore, there was no significant difference between the measured force and the force that would be predicted from the obtained perceptual bias.

Three Characteristics of Cheetah Galloping Improve Running Performance Through Spinal Movement: A Modeling Study.

Cheetahs are the fastest land animal. Their galloping shows three characteristics: small vertical movement of their center of mass, small whole-body pitching movement, and large spine bending movement. We hypothesize that these characteristics lead to enhanced gait performance in cheetahs, including higher gait speed. In this study, we used a simple model with a spine joint and torsional spring, which emulate the body flexibility, to verify our hypothesis from a dynamic perspective. Specifically, we numerically searched periodic solutions and evaluated what extent each solution shows the three characteristics. We then evaluated the gait performance and found that the solutions with the characteristics achieve high performances. This result supports our hypothesis. Furthermore, we revealed the mechanism for the high performances through the dynamics of the spine movement. These findings extend the current understanding of the dynamic mechanisms underlying high-speed locomotion in cheetahs.

Evaluation of the characteristics of various types of coils for the embolization of intracranial aneurysms with an optical pressure sensor system.

INTRODUCTION: In coil embolization for an intracranial aneurysm, it is important to appropriately choose the coil most suitable for coping with various unforeseen situations. Additionally, because dense coil packing of the aneurysm sac is the most important factor to avoid a recurrence, properly selecting the coil is essential. In this article, the authors measured the coil insertion pressure of various types of coils with a newly developed sensor system, and coil characteristics were investigated. METHODS: The sensor consists of a hemostatic valve connected to the proximal end of a microcatheter. The sensor principle is based on an optical system. Using this, an experimental silicone aneurysm embolization was performed automatically at constant speed. The pattern of the insertion pressure and the maximum insertion pressure (MIP) were analyzed for the various types of coils. The sensor continuously monitored the mechanical force during the insertions. RESULTS: The sensor adequately recorded the coil insertion pressure during embolization in each coil. MIP was generally ranked in order of the coil type. The soft type coils required relatively less insertion pressure than standard/helical and 3D type. As for the patterns of coil insertion pressure, each coil presented a saw-like pressure pattern, though we observed some slight differences. 3D type coils showed peak pressure at the moment of "painting". Coil loop diameters barely affected MIP. However, as to the patterns of pressure, larger size coils more often presented the peak. CONCLUSIONS: Coil characteristics were well evaluated. The results obtained here reflected some actual clinical experience. Furthermore, collecting the in vivo study is mandatory, which may provide clinically useful data.

A novel pressure sensor with an optical system for coil embolization of intracranial aneurysms. Laboratory investigation.

OBJECT: In endovascular coil embolization for an intracranial aneurysm, the excessive pressure created during coil insertion into an aneurysm can cause a catastrophic rupture or dislodge a microcatheter tip from the aneurysm dome, resulting in insufficient embolization. Such undue mechanical pressure can only be subjectively detected by the subtle tactile feedback the surgeon experiences. Therefore, the authors of this study developed a new sensor device to measure the coil insertion pressure via an optical system. METHODS: This novel sensor system consists of a hemostatic valve connected to the proximal end of a microcatheter (Y-connector). The sensor principle is based on an optical system composed of a light-emitting diode (LED) and a line sensor. The latter measures how much the coil-delivery wire slightly bends in response to the insertion pressure by detecting the wire shadow. This information is translated into a given force level. Experimental aneurysm embolization was performed using this optical sensor. A silicone aneurysm model and an in vivo model (porcine aneurysm model) were used in this study. Several surgeons manually performed the coil insertions. The sensor continuously monitored the mechanical force during the insertions. RESULTS: The sensor adequately recorded the coil insertion pressure during embolization. The presence of the sensor did not hinder the embolization procedure in any way. During embolization in the silicone aneurysm model, a sinusoid pattern of pressure occurred, reflecting actual clinical experience. Similar results were obtained in the in vivo study. CONCLUSIONS: This new sensor device adequately measures coil insertion pressure. This system provides potentially safer and more reliable aneurysm embolizations.

DNN-Based Assistant in Laparoscopic Computer-Aided Palpation.

Tactile sensory input of surgeons is severely limited in minimally invasive surgery, therefore manual palpation cannot be performed for intraoperative tumor detection. Computer-aided palpation, in which tactile information is acquired by devices and relayed to the surgeon, is one solution for overcoming this limitation. An important design factor is the method by which the acquired information is fed back to the surgeon. However, currently there is no systematic method for achieving this aim, and it is possible that a badly implemented feedback mechanism could adversely affect the performance of the surgeon. In this study, we propose an assistance algorithm for intraoperative tumor detection in laparoscopic surgery. Our scenario is that the surgeon manipulates a sensor probe, makes a decision based on the feedback provided from the sensor, while simultaneously, the algorithm analyzes the time series of the sensor output. Thus, the algorithm assists the surgeon in making decisions by providing independent detection results. A deep neural network model with three hidden layers was used to analyze the sensor output. We propose methods to input the time series of the sensor output to the model for real-time analysis, and to determine the criterion for detection by the model. This study aims to validate the feasibility of the algorithm by using data acquired in our previous psychophysical experiment. There, novice participants were asked to detect a phantom of an early-stage gastric tumor through visual feedback from the tactile sensor. In addition to the analysis of the accuracy, signal detection theory was employed to assess the potential detection performance of the model. The detection performance was compared with that of human participants. We conducted two types of validation, and found that the detection performance of the model was not significantly different from that of the human participants if the data from a known user was included in the model construction. The result supports the feasibility of the proposed algorithm for detection assistance in computer-aided palpation.

Author Correction: Role of extrinsic mechanical force in the development of the RA-I tactile mechanoreceptor.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Visual and tactile feedback for a direct-manipulating tactile sensor in laparoscopic palpation.

BACKGROUND: A surgeon's tactile sense can contribute to intraoperative tumor detection, but it is limited by laparoscopic surgery. METHODS: We have developed a simple and biocompatible tactile sensor. This study aimed to design and evaluate visual and tactile feedback from the sensor for laparoscopic tumor detection. A line graph was offered through a monitor as the visual feedback. A normal force was presented to the user's foot as the tactile feedback. Twelve novices conducted a task of detecting a phantom tumor under 4 conditions (no feedback, visual feedback, tactile feedback and a combination of both types of feedback). RESULTS: The visual feedback was significantly more effective in detection than no feedback. Moreover, both visual and tactile feedback led to safer manipulation with significantly smaller load and lower scanning speed, respectively. CONCLUSIONS: The results suggest that visual and tactile feedback can be useful for laparoscopic palpation; however, their effects depend on the means in which they are presented.

A Pneumatic Tactile Ring for Instantaneous Sensory Feedback in Laparoscopic Tumor Localization.

We aim to achieve intraoperative localization of an early-stage gastric tumor that cannot be visually detected during laparoscopic surgery. In this study, we developed and evaluated a pneumatic tactile ring, which is a clinically applicable tactile device to provide instantaneous feedback from a tactile sensor directly manipulated by a surgeon. It was designed to be worn on the finger of the manipulating hand and to present pressure to the finger pad. It is lightweight, cost-effective, disposable, and sterilizable. We also developed a compact pneumatic drive unit to control the pressure and investigated its fundamental performance. The bandwidth of the pressure control was at least 1.3 Hz with a controllable range of up to 79.7 kPa. Moreover, a psychophysical experiment was performed to obtain the Weber ratio of the pressure and evaluate the effectiveness of the instantaneous tactile feedback of the sensor output through the tactile ring. The Weber ratio was 0.40 at the reference pressure of 22.7 kPa. The provided tactile feedback significantly reduced the absolute localization error and increased participants' confidence in their answers. It was shown that the tactile feedback through the ring is effective in laparoscopic tumor localization.

Role of extrinsic mechanical force in the development of the RA-I tactile mechanoreceptor.

Rapidly adapting type I (RA-I) mechanoreceptors play an important role in sensing the low-frequency vibration aspects of touch. The structure of the RA-I mechanoreceptor is extremely complex regardless of its small size, limiting our understanding of its mechanotransduction. As a result of the emergence of bioengineering, we previously proposed an in vitro bioengineering approach for RA-I receptors to overcome this limitation. Currently, the in vitro bioengineering approach for the RA-I receptor is not realizable given the lack of knowledge of its morphogenesis. This paper demonstrates our first attempt to interpret the cellular morphogenesis of the RA-I receptor. We found indications of extrinsic mechanical force nearby the RA-I receptor in the developing fingertip. Using a mechanical compression device, the axon of dorsal root ganglion (DRG) neurons buckled in vitro into a profile that resembled the morphology of the RA-I receptor. This work encourages further implementation of this bioengineering approach in tactile receptor-related research.

Grasper having tactile sensing function using acoustic reflection for laparoscopic surgery.

PURPOSE: In current minimally invasive surgery techniques, the tactile information available to the surgeon is limited. Improving tactile sensation could enhance the operability of surgical instruments. Considering surgical applications, requirements such as having electrical safety, a simple structure, and sterilization capability should be considered. The current study sought to develop a grasper that can measure grasping force at the tip, based on a previously proposed tactile sensing method using acoustic reflection. This method can satisfy the requirements for surgical applications because it has no electrical element within the part that is inserted into the patient's body. METHODS: We integrated our acoustic tactile sensing method into a conventional grasping forceps instrument. We designed the instrument so that acoustic cavities within a grasping arm and a fork sleeve were connected by a small cavity in a pivoting joint. In this design, when the angle between the two grasping arms changes during grasping, the total length and local curvature of the acoustic cavity remain unchanged. Thus, the grasping force can be measured regardless of the orientation of the grasping arm. RESULTS: We developed a prototype sensorized grasper based on our proposed design. Fundamental tests revealed that sensor output increased with increasing contact force applied to the grasping arm, and the angle of the grasping arm did not significantly affect the sensor output. Moreover, the results of a grasping test, in which objects with different softness characteristics were held by the grasper, revealed that the grasping force could be appropriately adjusted to handle different objects on the basis of sensor output. CONCLUSIONS: Experimental results demonstrated that the prototype grasper can measure grasping force, enabling safe and stable grasping.

Effect of 3D microstructure of dermal papillae on SED concentration at a mechanoreceptor location.

The feeling of touch is an essential human sensation. Four types of mechanoreceptors (i.e., FA-I, SA-I, FA-II, and SA-II) in human skin signalize physical properties, such as shape, size, and texture, of an object that is touched and transmit the signal to the brain. Previous studies attempted to investigate the mechanical properties of skin microstructure and their effect on mechanoreceptors by using finite element modeling. However, very few studies have focused on the three-dimensional microstructure of dermal papillae, and this is related to that of FA-I receptors. A gap exists between conventional 2D models of dermal papillae and the natural configuration, which corresponds to a complex and uneven structure with depth. In this study, the three-dimensional microstructure of dermal papillae is modeled, and the differences between two-dimensional and three-dimensional aspects of dermal papillae on the strain energy density at receptor positions are examined. The three-dimensional microstructure has a focalizing effect and a localizing effect. Results also reveal the potential usefulness of these effects for tactile sensor design, and this may improve edge discrimination.

Two-Photon Imaging of DiO-Labelled Meissner Corpuscle in Living Mouse's Fingertip.

Meissner corpuscles are the fast adapting type I (FA-I) mechanoreceptor that locates at the dermal papillae of skin. The Meissner corpuscle is well known for its complex structure, consisting of spiral axons, lamellar cells, and a collagen capsule. Fluorescent microscopy has become a convenient method for observing the Meissner corpuscle and its inner structure. This method requires preparing samples with fingertip cross-sections and performing antibody staining before observation. Various kinds of microscopy can be used for observation, such as confocal microscopy, transmission electron microscopy (TEM), or scanning electron microscopy (SEM). Although the anatomical shape, distribution, and components of Meissner corpuscle are recognized, they have been mostly determined from observations of fixed tissues. Therefore, knowledge of mechanical transduction is limited by the lack of in vivo experiments and individual differences among samples. In this study, we propose a novel less invasive imaging method that incorporates a staining technique with lipophilic carbocyanine [Formula: see text] and two-photon microscopy. This combination allows us to repetitively observe the Meissner corpuscle in a living mouse.

Tactile sensor using acoustic reflection for lump detection in laparoscopic surgery.

PURPOSE: Laparoscopic surgery limits a surgeon's tactile sense. A tactile sensor could allow real-time tumor detection in laparoscopic surgery through lump inspection. This study was aimed at developing a simple and biocompatible tactile sensor for laparoscopic surgery. The proposed tactile sensor has a forceps-like shape, has no electrical elements in the tissue contact area, and can be sterilized and cleaned. METHODS: We developed a tactile sensor using acoustic reflection. It is composed of a handle with a speaker and a microphone, an aluminum tube, and a sensor tip with a deformable elastic cavity. The acoustic wave in the tube is the superposition of the input wave and two waves reflected at the closed edge and the projection generated by deformation due to contact with an object. By measuring the acoustic wave in the tube, information of the deformation is derived. RESULTS: The sensor is modeled, and the output is analyzed to determine design parameters of the sensor. Then, a prototype of the sensor is assembled. Fundamental experiments show that the sensor output increases with increasing normal deformation. Moreover, experiments using a phantom of the stomach wall with a 0-IIc type tumor (most common early stage gastric cancer) show that large sensor output is obtained for the lump when the sensor is moved across the back surface of the tumor. CONCLUSIONS: The theoretical and experimental results show that the sensor is sensitive to the deformation due to contact with an object and has the potential to detect a lump in laparoscopic surgery.

Contact force and scanning velocity during active roughness perception.

Haptic perception is bidirectionally related to exploratory movements, which means that exploration influences perception, but perception also influences exploration. We can optimize or change exploratory movements according to the perception and/or the task, consciously or unconsciously. This paper presents a psychophysical experiment on active roughness perception to investigate movement changes as the haptic task changes. Exerted normal force and scanning velocity are measured in different perceptual tasks (discrimination or identification) using rough and smooth stimuli. The results show that humans use a greater variation in contact force for the smooth stimuli than for the rough stimuli. Moreover, they use higher scanning velocities and shorter break times between stimuli in the discrimination task than in the identification task. Thus, in roughness perception humans spontaneously use different strategies that seem effective for the perceptual task and the stimuli. A control task, in which the participants just explore the stimuli without any perceptual objective, shows that humans use a smaller contact force and a lower scanning velocity for the rough stimuli than for the smooth stimuli. Possibly, these strategies are related to aversiveness while exploring stimuli.

Development of a real-time tactile sensing system for brain tumor diagnosis.

PURPOSE: Tactile sensing techniques may distinguish tumor from healthy tissue and have potential for intraoperative brain tumor diagnosis. The aim of this study is to develop a biocompatible real-time sensing system to measure tactile information such as softness and smoothness, and its application to brain tumor diagnosis. METHODS: An active tactile sensor is developed using balloon expansion. This compact system provides instantaneous tactile information and has potential for brain tumor diagnosis. Measurements are obtained on soft samples with different stiffness and surface condition with testing of boundary condition influence on thickness and area of the object. Then, measurements on white matter and gray matter of porcine ex vivo brain are done as the first step for brain tumor diagnosis. RESULTS: The sensor can discriminate samples with different stiffness and surface condition subject to influence by boundary conditions. The sensor can evaluate an object relatively under the same boundary conditions but requires enough thickness and area to evaluate absolutely. Measurements on brain show that the sensor can discriminate between white matter and gray matter. CONCLUSIONS: Although the sensor has problems on absolute evaluation, results show that the sensor can evaluate tactile information, and it has potential for brain tumor diagnosis.